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Kavitha SJ, Panchanatheswaran K, Elsegood MRJ, Dale SH, Yuen VG, McNeill JH. Synthesis, characterization and glucose-lowering studies of air-stable, mixed-ligand vanadium(III) acetylacetonates and oxidovanadium(IV) complexes containing pyridine-based ligands. J Inorg Biochem 2025; 270:112929. [PMID: 40414195 DOI: 10.1016/j.jinorgbio.2025.112929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 04/11/2025] [Accepted: 04/16/2025] [Indexed: 05/27/2025]
Abstract
The glucose-lowering properties of five acetylacetonate complexes of vanadium(III) containing picolinate (pyridine-2-carboxylate)/1,10-phenanthroline/2,2'-bipyridyl as co-ligands and three oxidovanadium(IV) complexes have been examined by in vivo experiments on the streptozotozin (STZ)-diabetic rat model and compared against the benchmark compound, bis(maltolato)oxidovanadium(IV). The bipyridyl and the picolinate complexes exhibit more significant activities than the phenanthroline complexes. The single crystal X-ray structures of three new complexes (acetylacetonato)bis(pyridine-2-carboxylato)vanadium(III), bis(methanol)(pyridine-2,6-dicarboxylato)oxidovanadium(IV) and (acetylacetonato)(1,10-phenanthroline)(thiocyanato)oxidovanadium(IV) are established in this work. The syntheses, spectral and electrochemical properties of all the complexes are discussed.
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Affiliation(s)
| | | | - Mark R J Elsegood
- Chemistry Department, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK
| | - Sophie H Dale
- Chemistry Department, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK
| | - Violet G Yuen
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
| | - John H McNeill
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada
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Mora-Rodriguez R, Moreno-Cabañas A, Alvarez-Jimenez L, Mora-Gonzalez D, Morales-Palomo F. High-Intensity Intervallic Exercise (HIIE) Is Superior to Isocaloric Moderate-Intensity Continuous Exercise (MICE) at Reducing Postprandial Hyperglycemia. Med Sci Sports Exerc 2025; 57:1019-1031. [PMID: 39661748 DOI: 10.1249/mss.0000000000003625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
PURPOSE We investigated if a bout of high-intensity intervallic exercise (HIIE) is more efficacious at reducing postprandial hyperglycemia than an isocaloric bout of moderate-intensity continuous exercise (MICE). METHODS Nineteen healthy physically active individuals (21% women) completed three trials in a randomized order: i ) HIIE cycling consisting of five bouts of 4 min at 83 ± 9% of subjects' maximal oxygen consumption ( O 2MAX ) with active recoveries at 53 ± 8%, for a total of 50 min; ii ) MICE cycling at 65 ± 8% of O 2max for 50 min; and iii ) CONTROL no exercise. All trials were followed by a standard oral glucose tolerance test (OGTT) ingesting 74 g of glucose traced with 1 g of uniformly labeled [ 13 C]-glucose. Plasma glucose and insulin concentrations, and plasma glucose kinetics ([6,6 2 H 2 ] glucose infusion) were measured before exercise, during exercise, and during the OGTT. Insulin sensitivity was estimated by the Matsuda index (ISI). Energy expenditure and carbohydrate oxidation (CHOxid) were monitored. RESULTS At rest, blood glucose, insulin concentrations, and CHOxid were similar in all three trials. During exercise, energy expenditure was similar in HIIE versus MICE (548 ± 131 vs 560 ± 125 kcal; P = 0.340). However, CHOxid, plasma glucose concentration, and its rates of appearance in plasma (Ra) were higher in HIIE versus MICE (Ra glucose 34.3 ± 9.8 vs 28.9 ± 6.8 μmol·kg -1 ·min -1 ; P = 0.021). During the OGTT, plasma glucose and insulin concentrations were lower, and insulin sensitivity was higher in HIIE versus CONTROL (ISI MATSUDA ; 12.4 ± 4.7 vs 10.8 ± 4.7 au; P = 0.007). Exercise delayed blood incorporation of [ 13 C]-glucose into blood ( P = 0.023). Early during the OGTT, glucose clearance rates were higher in HIIE versus CONTROL (7.1 ± 3.1 vs 5.5 ± 3.0 mL·kg -1 ·min -1 ; P = 0.015). CONCLUSIONS HIIE is more effective than MICE to reduce hyperglycemia and hyperinsulinemia after glucose ingestion. HIIE improves glycemic control by increasing splanchnic glucose retention and glucose clearance rates.
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Affiliation(s)
- Ricardo Mora-Rodriguez
- Exercise Physiology Lab at Toledo, Faculty of Sport Sciences, University of Castilla-La Mancha, Toledo, SPAIN
| | | | | | - Diego Mora-Gonzalez
- Grupo IMCU, Department of Nursing, Physiotherapy, and Occupational Therapy, University of Castilla-La Mancha, Toledo, SPAIN
| | - Felix Morales-Palomo
- Exercise Physiology Lab at Toledo, Faculty of Sport Sciences, University of Castilla-La Mancha, Toledo, SPAIN
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Ramezan M, Arzhang P, Shin AC. Milk-derived bioactive peptides in insulin resistance and type 2 diabetes. J Nutr Biochem 2025; 138:109849. [PMID: 39870329 DOI: 10.1016/j.jnutbio.2025.109849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 01/18/2025] [Accepted: 01/24/2025] [Indexed: 01/29/2025]
Abstract
Diabetes is a global health issue affecting over 6% of the world and 11% of the US population. It is closely linked to insulin resistance, a pivotal factor in Type 2 diabetes development. This review explores a promising avenue for addressing insulin resistance through the lens of Milk-Derived Bioactive Peptides (MBAPs). Taken from casein or whey fractions of various milks, MBAPs exhibit diverse health-promoting properties. Specific interactions between these peptides and enzymes involved in glucose digestion and metabolism have been examined, leading to the identification of some key peptides exerting the effects. This review emphasizes the positive impact of MBAPs on glycemic control through various mechanisms. Different cell lines have been used to investigate MBAPs' effects on insulin signaling, inflammation, and oxidative stress. Preclinical in vivo studies have also shown that MBAPs lower glucose, stimulate insulin, and reduce inflammation. Human trials further substantiate these findings and suggest the potential utility of milk protein hydrolysates containing MBAPs in individuals with insulin resistance or T2D to improve insulin action and glucose homeostasis.
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Affiliation(s)
- Marjan Ramezan
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Health & Human Sciences, Texas Tech University, Lubbock, Texas, USA
| | - Pishva Arzhang
- Qods Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Andrew C Shin
- Neurobiology of Nutrition Laboratory, Department of Nutritional Sciences, College of Health & Human Sciences, Texas Tech University, Lubbock, Texas, USA.
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Shekoohi N, Carson BP, Fitzgerald RJ. Antioxidative, Glucose Management, and Muscle Protein Synthesis Properties of Fish Protein Hydrolysates and Peptides. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:21301-21317. [PMID: 39297866 PMCID: PMC11450812 DOI: 10.1021/acs.jafc.4c02920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 08/30/2024] [Accepted: 09/11/2024] [Indexed: 10/03/2024]
Abstract
The marine environment is an excellent source for many physiologically active compounds due to its extensive biodiversity. Among these, fish proteins stand out for their unique qualities, making them valuable in a variety of applications due to their diverse compositional and functional properties. Utilizing fish and fish coproducts for the production of protein hydrolysates and bioactive peptides not only enhances their economic value but also reduces their potential environmental harm, if left unutilized. Fish protein hydrolysates (FPHs), known for their excellent nutritional value, favorable amino acid profiles, and beneficial biological activities, have generated significant interest for their potential health benefits. These hydrolysates contain bioactive peptides which are peptide sequences known for their beneficial physiological effects. These biologically active peptides play a role in metabolic regulation/modulation and are increasingly seen as promising ingredients in functional foods, nutraceuticals and pharmaceuticals, with potential to improve human health and prevent disease. This review aims to summarize the current in vitro, cell model (in situ) and in vivo research on the antioxidant, glycaemic management and muscle health enhancement properties of FPHs and their peptides.
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Affiliation(s)
- Niloofar Shekoohi
- Department
of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland
| | - Brian P. Carson
- Department
of Physical Education and Sport Sciences, Faculty of Education and
Health Sciences, University of Limerick, V94 T9PX Limerick, Ireland
- Health
Research Institute, University of Limerick, V94 T9PX Limerick, Ireland
| | - Richard J. Fitzgerald
- Department
of Biological Sciences, University of Limerick, V94 T9PX Limerick, Ireland
- Health
Research Institute, University of Limerick, V94 T9PX Limerick, Ireland
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Anyiam O, Abdul Rashid RS, Bhatti A, Khan-Madni S, Ogunyemi O, Ardavani A, Idris I. A Systematic Review and Meta-Analysis of the Effect of Caloric Restriction on Skeletal Muscle Mass in Individuals with, and without, Type 2 Diabetes. Nutrients 2024; 16:3328. [PMID: 39408294 PMCID: PMC11479040 DOI: 10.3390/nu16193328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. METHODS EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). RESULTS Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. CONCLUSIONS Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.
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Affiliation(s)
- Oluwaseun Anyiam
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
| | | | - Aniqah Bhatti
- Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK
| | - Saif Khan-Madni
- School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
| | - Olakunmi Ogunyemi
- Department of Acute Medicine, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
- Nuffield Department of Population Health, University of Oxford, Oxford OX1 2JD, UK
| | - Arash Ardavani
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
| | - Iskandar Idris
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
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Mizukami H. Pathological evaluation of the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy. Pathol Int 2024; 74:438-453. [PMID: 38888200 PMCID: PMC11551828 DOI: 10.1111/pin.13458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/29/2024] [Accepted: 06/02/2024] [Indexed: 06/20/2024]
Abstract
Currently, there are more than 10 million patients with diabetes mellitus in Japan. Therefore, the need to explore the pathogenesis of diabetes and the complications leading to its cure is becoming increasingly urgent. Pathological examination of pancreatic tissues from patients with type 2 diabetes reveals a decrease in the volume of beta cells because of a combination of various stresses. In human type 2 diabetes, islet amyloid deposition is a unique pathological change characterized by proinflammatory macrophage (M1) infiltration into the islets. The pathological changes in the pancreas with islet amyloid were different according to clinical factors, which suggests that type 2 diabetes can be further subclassified based on islet pathology. On the other hand, diabetic peripheral neuropathy is the most frequent diabetic complication. In early diabetic peripheral neuropathy, M1 infiltration in the sciatic nerve evokes oxidative stress or attenuates retrograde axonal transport, as clearly demonstrated by in vitro live imaging. Furthermore, islet parasympathetic nerve density and beta cell volume were inversely correlated in type 2 diabetic Goto-Kakizaki rats, suggesting that diabetic peripheral neuropathy itself may contribute to the decrease in beta cell volume. These findings suggest that the pathogenesis of diabetes mellitus and diabetic peripheral neuropathy may be interrelated.
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Affiliation(s)
- Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Biomedical Research CenterHirosaki University Graduate School of MedicineHirosakiAomoriJapan
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Anyiam O, Phillips B, Quinn K, Wilkinson D, Smith K, Atherton P, Idris I. Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus. Clin Nutr 2024; 43:1907-1913. [PMID: 38996661 DOI: 10.1016/j.clnu.2024.06.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 06/26/2024] [Indexed: 07/14/2024]
Abstract
BACKGROUND & AIMS Very-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. METHODS Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. RESULTS Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01). CONCLUSION VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.
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Affiliation(s)
- Oluwaseun Anyiam
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK; Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, DE22 3NE, UK
| | - Bethan Phillips
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Katie Quinn
- College of Agriculture, Food & Nutrition, University College Dublin, Ireland
| | - Daniel Wilkinson
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Kenneth Smith
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK
| | - Philip Atherton
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK.
| | - Iskandar Idris
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK; Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, DE22 3NE, UK.
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Huang C, Chen X, Ouyang Z, Meng L, Liu J, Pang Q, Fan R. Bisphenol a accelerates the glucolipotoxicity-induced dysfunction of rat insulinoma cell lines: An implication for a potential risk of environmental bisphenol a exposure for individuals susceptible to type 2 diabetes. Toxicol In Vitro 2024; 99:105866. [PMID: 38844119 DOI: 10.1016/j.tiv.2024.105866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/21/2024] [Accepted: 06/03/2024] [Indexed: 06/11/2024]
Abstract
Epidemiological studies have suggested a correlation between bisphenol A (BPA) and type 2 diabetes (T2DM). The effects of BPA on β-cell dysfunction may reveal the risks from an in vitro perspective. We used the rat insulinoma (INS-1) cell lines (a type of β-cells) to set up normal or damaged models (DM), which were exposed to various concentrations of BPA (0.001, 0.01, 0.1, 1, 10 and 100 μM). An increase in reactive oxygen species (ROS) and apoptosis, and a decrease in cell viability were observed in INS-1 cells exposed to high doses of BPA for 48 h. Interestingly, exposure to lower doses of BPA for 24 h resulted in increased ROS levels and apoptosis rates in INS-1 in the DM group, along with decreased cell viability, suggesting that BPA exerts toxicity to INS-1 cells, particularly to the DM group. Insulin levels and Glut2 expression, glucose consumption, intracellular Ca2+ and insulin secretion were increased in INS-1 cells after 48 h exposure to high dose of BPA. Stronger effects were observed in the DM group, even those exposed to low doses of BPA for 24 h. Moreover, BPA inhibited high glucose-stimulated insulin secretion in these cells. Our research suggests that low doses of BPA exacerbate the dysfunction caused by glucolipotoxicity, implying environmental BPA exposure poses a risk for individuals with prediabetes or T2DM.
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Affiliation(s)
- Chengmeng Huang
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Xiaolin Chen
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Zedong Ouyang
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Lingxue Meng
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Jian Liu
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China
| | - Qihua Pang
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China.
| | - Ruifang Fan
- Guangzhou Key Laboratory of Subtropical Biodiversity and Biomonitoring, Guangdong Provincial Engineering Technology Research Center for Drug and Food Biological Resources Processing and Comprehensive Utilization, School of Life Sciences, South China Normal University, Guangzhou 510631, China.
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Lee SB, Woo TW, Baek DC, Son CG. A standardized herbal combination of Astragalus membranaceus and Paeonia japonica promotes skeletal muscle hypertrophy in a treadmill exercise mouse model. Front Nutr 2024; 11:1362550. [PMID: 38966418 PMCID: PMC11223055 DOI: 10.3389/fnut.2024.1362550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 05/29/2024] [Indexed: 07/06/2024] Open
Abstract
Background Maintaining a normal range of muscle mass and function is crucial not only for sustaining a healthy life but also for preventing various disorders. Numerous nutritional or natural resources are being explored for their potential muscle hypertrophic properties. Aim We aimed to evaluate the muscle hypertrophic effects of APX, a 1:1 mixture of Astragalus membranaceus and Paeonia japonica. In addition to the myotube differentiation cell assay, we utilized a weighted exercise-based animal model and evaluated changes in muscle hypertrophy using dual-energy X-ray absorptiometry (DXA) and histological analysis. Results The 8-week treadmill exercise led to notable decreases in body weight and fat mass but an increase in muscle mass compared to the control group. Administration of APX significantly accelerated muscle mass gain (p < 0.05) without altering body weight or fat mass compared to the exercise-only group. This muscle hypertrophic effect of APX was consistent with the histologic size of muscle fibers in the gastrocnemius (p > 0.05) and rectus femoris (p < 0.05), as well as the regulation of myogenic transcription factors (MyoD and myogenin), respectively. Furthermore, APX demonstrated a similar action to insulin-like growth factor 1, influencing the proliferation of C2C12 myoblast cells (p < 0.01) and their differentiation into myotubes (p < 0.05) compared to the control group. Conclusion The present study provides experimental evidence that APX has muscle hypertrophic effects, and its underlying mechanisms would involve the modulation of MyoD and myogenin.
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Affiliation(s)
| | | | | | - Chang-Gue Son
- Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon, Republic of Korea
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10
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Voigt JH, Lauritsen KM, Pedersen SB, Hansen TK, Møller N, Jessen N, Laurenti MC, Dalla Man C, Vella A, Gormsen LC, Søndergaard E. Four weeks SGLT2 inhibition improves beta cell function and glucose tolerance without affecting muscle free fatty acid or glucose uptake in subjects with type 2 diabetes. Basic Clin Pharmacol Toxicol 2024; 134:643-656. [PMID: 38409617 DOI: 10.1111/bcpt.13991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 01/25/2024] [Accepted: 02/06/2024] [Indexed: 02/28/2024]
Abstract
AIMS Sodium glucose co-transporter-2 (SGLT2) inhibition lowers glucose levels independently of insulin, leading to reduced insulin secretion and increased lipolysis, resulting in elevated circulating free fatty acids (FFAs). While SGLT2 inhibition improves tissue insulin sensitivity, the increase in circulating FFAs could reduce insulin sensitivity in skeletal muscle and the liver. We aimed to investigate the effects of SGLT2 inhibition on substrate utilization in skeletal muscle and the liver and to measure beta-cell function and glucose tolerance. METHODS Thirteen metformin-treated individuals with type 2 diabetes were randomized to once-daily empagliflozin 25 mg or placebo for 4 weeks in a crossover design. Skeletal muscle glucose and FFA uptake together with hepatic tissue FFA uptake were measured using [18F]FDG positron emission tomography/computed tomography (PET/CT) and [11C]palmitate PET/CT. Insulin secretion and action were estimated using the oral minimal model. RESULTS Empagliflozin did not affect glucose (0.73 ± 0.30 vs. 1.16 ± 0.64, μmol/g/min p = 0.11) or FFA (0.60 ± 0.30 vs. 0.56 ± 0.3, μmol/g/min p = 0.54) uptake in skeletal muscle. FFA uptake in the liver (21.2 ± 10.1 vs. 19 ± 8.8, μmol/100 ml/min p = 0.32) was unaffected. Empagliflozin increased total beta-cell responsivity (20 ± 8 vs. 14 ± 9, 10-9 min-1, p < 0.01) and glucose effectiveness (2.6 × 10-2 ± 0.3 × 10-2 vs. 2.4 × 10-2 ± 0.3 × 10-2, dL/kg/min, p = 0.02). CONCLUSIONS Despite improved beta-cell function and glucose tolerance, empagliflozin does not appear to affect skeletal muscle FFA or glucose uptake.
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Affiliation(s)
| | - Katrine M Lauritsen
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
| | - Steen Bønløkke Pedersen
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | | | - Niels Møller
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Niels Jessen
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Marcello C Laurenti
- Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
| | - Chiara Dalla Man
- Department of Information Engineering, University of Padua, Padua, Italy
| | - Adrian Vella
- Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
| | - Lars C Gormsen
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Esben Søndergaard
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
- Endocrine Research Unit, Department of Endocrinology, Diabetes and Nutrition, Mayo Clinic, Rochester, Minnesota, USA
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Mora-Rodriguez R, Moreno-Cabañas A, Alvarez-Jimenez L, Mora-Gonzalez D, Ortega JF, Morales-Palomo F. A bout of aerobic exercise in the heat increases carbohydrate use but does not enhance the disposal of an oral glucose load, in healthy active individuals. Am J Physiol Endocrinol Metab 2024; 326:E648-E662. [PMID: 38568152 DOI: 10.1152/ajpendo.00312.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 03/01/2024] [Accepted: 03/24/2024] [Indexed: 05/01/2024]
Abstract
We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating carbohydrate oxidation and glycogen use would increase the disposal of an ingested glucose load [i.e., oral glucose tolerance test (OGTT); 75 g of glucose]. Separated by at least 1 wk, nine young healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58 ± 5% V̇o2max either in a thermoneutral (21 ± 1°C; NEUTRAL) or in a hot environment (33 ± 1°C; HEAT) eliciting similar energy expenditure (503 ± 101 kcal). These two trials were compared with a no-exercise trial (NO EXER). Twenty minutes after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149 ± 35 vs. 124 ± 31 µmol·kg-1·min-1, P = 0.010). However, during the following OGTT, glucose Rd was similar in HEAT and NEUTRAL trials (i.e., 25.1 ± 3.6 vs. 25.2 ± 5.3 µmol·kg-1·min-1, P = 0.981). Insulin sensitivity (i.e., ISIndexMATSUDA) only improved in NEUTRAL compared with NO EXER (10.1 ± 4.6 vs. 8.8 ± 3.7 au; P = 0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT.NEW & NOTEWORTHY Exercise in the heat increases estimated muscle glycogen use. Reduced muscle glycogen after exercise in the heat could increase insulin-mediated glucose uptake during a subsequent oral glucose tolerance test (OGTT). However, plasma glucose kinetics are not improved during the OGTT in response to a bout of exercise in the heat, and insulin sensitivity worsens. Heat stress activates glucose counterregulatory hormones whose actions may linger during the OGTT, preventing increased glucose uptake.
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Affiliation(s)
| | - Alfonso Moreno-Cabañas
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
- Centre for Nutrition, Exercise and Metabolism, University of Bath, Bath, United Kingdom
- Department for Health, University of Bath, Bath, United Kingdom
| | | | - Diego Mora-Gonzalez
- Department of Nursing, Physiotherapy, and Occupational Therapy, University of Castilla-La Mancha, Toledo, Spain
| | - Juan Fernando Ortega
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
| | - Felix Morales-Palomo
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
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12
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Ma J, Gao R, Xie Q, Pan X, Tong N. Whole transcriptome sequencing analyses of islets reveal ncRNA regulatory networks underlying impaired insulin secretion and increased β-cell mass in high fat diet-induced diabetes mellitus. PLoS One 2024; 19:e0300965. [PMID: 38557554 PMCID: PMC10984535 DOI: 10.1371/journal.pone.0300965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 03/07/2024] [Indexed: 04/04/2024] Open
Abstract
AIM Our study aims to identify novel non-coding RNA-mRNA regulatory networks associated with β-cell dysfunction and compensatory responses in obesity-related diabetes. METHODS Glucose metabolism, islet architecture and secretion, and insulin sensitivity were characterized in C57BL/6J mice fed on a 60% high-fat diet (HFD) or control for 24 weeks. Islets were isolated for whole transcriptome sequencing to identify differentially expressed (DE) mRNAs, miRNAs, IncRNAs, and circRNAs. Regulatory networks involving miRNA-mRNA, lncRNA-mRNA, and lncRNA-miRNA-mRNA were constructed and functions were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS Despite compensatory hyperinsulinemia and a significant increase in β-cell mass with a slow rate of proliferation, HFD mice exhibited impaired glucose tolerance. In isolated islets, insulin secretion in response to glucose and palmitic acid deteriorated after 24 weeks of HFD. Whole transcriptomic sequencing identified a total of 1324 DE mRNAs, 14 DE miRNAs, 179 DE lncRNAs, and 680 DE circRNAs. Our transcriptomic dataset unveiled several core regulatory axes involved in the impaired insulin secretion in HFD mice, such as miR-6948-5p/Cacna1c, miR-6964-3p/Cacna1b, miR-3572-5p/Hk2, miR-3572-5p/Cckar and miR-677-5p/Camk2d. Additionally, proliferative and apoptotic targets, including miR-216a-3p/FKBP5, miR-670-3p/Foxo3, miR-677-5p/RIPK1, miR-802-3p/Smad2 and ENSMUST00000176781/Caspase9 possibly contribute to the increased β-cell mass in HFD islets. Furthermore, competing endogenous RNAs (ceRNA) regulatory network involving 7 DE miRNAs, 15 DE lncRNAs and 38 DE mRNAs might also participate in the development of HFD-induced diabetes. CONCLUSIONS The comprehensive whole transcriptomic sequencing revealed novel non-coding RNA-mRNA regulatory networks associated with impaired insulin secretion and increased β-cell mass in obesity-related diabetes.
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Affiliation(s)
- Jinfang Ma
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
- Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China
| | - Rui Gao
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Qingxing Xie
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
- Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaohui Pan
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
- Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China
| | - Nanwei Tong
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
- Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China
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13
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Skurk T, Bosy-Westphal A, Grünerbel A, Kabisch S, Keuthage W, Kronsbein P, Müssig K, Nussbaumer H, Pfeiffer AFH, Simon MC, Tombek A, Weber KS, Rubin D. Dietary Recommendations for Persons with Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes 2024; 132:182-215. [PMID: 38286422 DOI: 10.1055/a-2166-6772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2024]
Affiliation(s)
- Thomas Skurk
- ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany
| | - Anja Bosy-Westphal
- Institute of Human Nutrition, Faculty of Agriculture and Nutritional Sciences, Christian-Albrechts University of Kiel, Kiel, Germany
| | | | - Stefan Kabisch
- German Institute of Human Nutrition Potsdam-Rehbrücke, Potsdam, Germany
- German Center for Diabetes Research (DZD), Munich, Germany
| | - Winfried Keuthage
- Specialist Practice for Diabetes and Nutritional Medicine, Münster, Germany
| | - Peter Kronsbein
- Faculty of Nutrition and Food Sciences, Niederrhein University of Applied Sciences, Mönchengladbach Campus, Mönchengladbach, Germany
| | - Karsten Müssig
- Department of Internal Medicine, Gastroenterology and Diabetology, Niels Stensen Hospitals, Franziskus Hospital Harderberg, Georgsmarienhütte, Germany
| | | | - Andreas F H Pfeiffer
- Department of Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Marie-Christine Simon
- Institute of Nutrition and Food Sciences, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | - Astrid Tombek
- Diabetes Centre Bad Mergentheim, Bad Mergentheim, Germany
| | - Katharina S Weber
- Institute for Epidemiology, Christian-Albrechts University of Kiel, Kiel, Germany
| | - Diana Rubin
- Vivantes Hospital Spandau, Berlin, Germany
- Vivantes Humboldt Hospital, Berlin, Germany
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14
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Wang Y, Hong X, Cao W, Lv J, Yu C, Huang T, Sun D, Liao C, Pang Y, Pang Z, Yu M, Wang H, Wu X, Liu Y, Gao W, Li L. Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study. J Endocrinol Invest 2024; 47:535-546. [PMID: 37524979 DOI: 10.1007/s40618-023-02164-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 07/24/2023] [Indexed: 08/02/2023]
Abstract
PURPOSE Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.
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Affiliation(s)
- Y Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - X Hong
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - W Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - J Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - C Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - T Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - D Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - C Liao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Y Pang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Z Pang
- Qingdao Center for Disease Control and Prevention, Qingdao, China
| | - M Yu
- Zhejiang Center for Disease Control and Prevention, Hangzhou, China
| | - H Wang
- Jiangsu Center for Disease Control and Prevention, Nanjing, China
| | - X Wu
- Sichuan Center for Disease Control and Prevention, Chengdu, China
| | - Y Liu
- Heilongjiang Center for Disease Control and Prevention, Harbin, China
| | - W Gao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
| | - L Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
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15
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Boyd ED, Zhang L, Ding G, Li L, Lu M, Li Q, Huang R, Kaur J, Hu J, Chopp M, Zhang Z, Jiang Q. The Glymphatic Response to the Development of Type 2 Diabetes. Biomedicines 2024; 12:401. [PMID: 38398003 PMCID: PMC10886551 DOI: 10.3390/biomedicines12020401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/21/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
The glymphatic system has recently been shown to be important in neurological diseases, including diabetes. However, little is known about how the progressive onset of diabetes affects the glymphatic system. The aim of this study is to investigate the glymphatic system response to the progressive onset of diabetes in a rat model of type 2 diabetic mellitus. Male Wistar rats (n = 45) with and without diabetes were evaluated using MRI glymphatic tracer kinetics, functional tests, and brain tissue immunohistochemistry. Our data demonstrated that the contrast agent clearance impairment gradually progressed with the diabetic duration. The MRI data showed that an impairment in contrast clearance occurred prior to the cognitive deficits detected using functional tests and permitted the detection of an early DM stage compared to the immuno-histopathology and cognitive tests. Additionally, the quantitative MRI markers of brain waste clearance demonstrated region-dependent sensitivity in glymphatic impairment. The improved sensitivity of MRI markers in the olfactory bulb and the whole brain at an early DM stage may be attributed to the important role of the olfactory bulb in the parenchymal efflux pathway. MRI can provide sensitive quantitative markers of glymphatic impairment during the progression of DM and can be used as a valuable tool for the early diagnosis of DM with a potential for clinical application.
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Affiliation(s)
- Edward D. Boyd
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Radiology, Michigan State University, East Lansing, MI 48824, USA
| | - Li Zhang
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
| | - Guangliang Ding
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Radiology, Michigan State University, East Lansing, MI 48824, USA
| | - Lian Li
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA;
| | - Qingjiang Li
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
| | - Rui Huang
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
| | - Jasleen Kaur
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Physics, Oakland University, Rochester, MI 48309, USA
| | - Jiani Hu
- Department of Radiology, Wayne State University, Detroit, MI 48202, USA;
| | - Michael Chopp
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Physics, Oakland University, Rochester, MI 48309, USA
- Department of Neurology, Wayne State University, Detroit, MI 28202, USA
| | - Zhenggang Zhang
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Neurology, Wayne State University, Detroit, MI 28202, USA
| | - Quan Jiang
- Department of Neurology, Henry Ford Health System, E&R B126, 2799 West Grand Boulevard, Detroit, MI 48202, USA; (L.Z.); (G.D.); (L.L.); (Q.L.); (J.K.); (M.C.); (Z.Z.); (Q.J.)
- Department of Radiology, Michigan State University, East Lansing, MI 48824, USA
- Department of Physics, Oakland University, Rochester, MI 48309, USA
- Department of Neurology, Wayne State University, Detroit, MI 28202, USA
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16
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Li X, Petrov MS. Dietary Fibre for the Prevention of Post-Pancreatitis Diabetes Mellitus: A Review of the Literature and Future Research Directions. Nutrients 2024; 16:435. [PMID: 38337719 PMCID: PMC10857198 DOI: 10.3390/nu16030435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/30/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
Post-pancreatitis diabetes mellitus-the most common sequela of pancreatitis-leads to poorer glycaemic control compared with type 2 diabetes. Because post-pancreatitis diabetes mellitus is an exemplar of secondary diabetes (with a clear underlying cause), much post-pancreatitis diabetes mellitus is preventable or treatable early. Earlier literature established the important role of dietary fibre in reducing plasma glucose in individuals with type 2 diabetes. The present review benchmarks available evidence on the role of habitual dietary fibre intake in pancreatitis and post-pancreatitis diabetes mellitus. It also paves the way for future research on the use of dietary fibre in the post-pancreatitis setting.
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Affiliation(s)
| | - Maxim S. Petrov
- School of Medicine, University of Auckland, Auckland 1023, New Zealand
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17
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Khoshnoudi P, Sabiza S, Khosravi M, Mohamadian B. Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats. Int J Exp Pathol 2024; 105:13-20. [PMID: 37969023 PMCID: PMC10797421 DOI: 10.1111/iep.12496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 09/23/2023] [Accepted: 10/21/2023] [Indexed: 11/17/2023] Open
Abstract
Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed. The monocytes were isolated from blood samples using the plastic adherence method and were exposed to dexamethasone (5-10 μ) for 24 h. Subsequently, they were washed with PBS and incubated in fresh cell culture medium for 5 days. The differentiated M2 cells were injected into four points of the experimental ulcers of the treatment group. Macroscopic and microscopic changes were evaluated and compared over a period of two weeks between the test and control groups. The infusion of these cells a few days after wounding enhances wound healing parameters significantly, as evidenced by an increase in germinating tissue formation, wound contraction, inflammation reduction, and collagen increase in the treated group.
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Affiliation(s)
- Parmis Khoshnoudi
- Department of Clinical Sciences, Faculty of Veterinary MedicineShahid Chamran University of AhvazAhvazIran
| | - Soroush Sabiza
- Department of Clinical Sciences, Faculty of Veterinary MedicineShahid Chamran University of AhvazAhvazIran
| | - Mohammad Khosravi
- Department of Pathobiology, Faculty of Veterinary MedicineShahid Chamran University of AhvazAhvazIran
| | - Babak Mohamadian
- Department of Pathobiology, Faculty of Veterinary MedicineShahid Chamran University of AhvazAhvazIran
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18
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Nada AA, Metwally AM, Asaad AM, Celik I, Ibrahim RS, Eldin SMS. Synergistic effect of potential alpha-amylase inhibitors from Egyptian propolis with acarbose using in silico and in vitro combination analysis. BMC Complement Med Ther 2024; 24:65. [PMID: 38291462 PMCID: PMC10826043 DOI: 10.1186/s12906-024-04348-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 01/11/2024] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND Type 2 Diabetes mellitus (DM) is an affliction impacting the quality of life of millions of people worldwide. An approach used in the management of Type 2 DM involves the use of the carbohydrate-hydrolyzing enzyme inhibitor, acarbose. Although acarbose has long been the go-to drug in this key approach, it has become apparent that its side effects negatively impact patient adherence and subsequently, therapeutic outcomes. Similar to acarbose in its mechanism of action, bee propolis, a unique natural adhesive biomass consisting of biologically active metabolites, has been found to have antidiabetic potential through its inhibition of α-amylase. To minimize the need for ultimately novel agents while simultaneously aiming to decrease the side effects of acarbose and enhance its efficacy, combination drug therapy has become a promising pharmacotherapeutic strategy and a focal point of this study. METHODS Computer-aided molecular docking and molecular dynamics (MD) simulations accompanied by in vitro testing were used to mine novel, pharmacologically active chemical entities from Egyptian propolis to combat Type 2 DM. Glide docking was utilized for a structure-based virtual screening of the largest in-house library of Egyptian propolis metabolites gathered from literature, in addition to GC-MS analysis of the propolis sample under investigation. Thereafter, combination analysis by means of fixed-ratio combinations of acarbose with propolis and the top chosen propolis-derived phytoligand was implemented. RESULTS Aucubin, identified for the first time in propolis worldwide and kaempferol were the most promising virtual hits. Subsequent in vitro α-amylase inhibitory assay demonstrated the ability of these hits to significantly inhibit the enzyme in a dose-dependent manner with an IC50 of 2.37 ± 0.02 mM and 4.84 ± 0.14 mM, respectively. The binary combination of acarbose with each of propolis and kaempferol displayed maximal synergy at lower effect levels. Molecular docking and MD simulations revealed a cooperative binding mode between kaempferol and acarbose within the active site. CONCLUSION The suggested strategy seems imperative to ensure a steady supply of new therapeutic entities sourced from Egyptian propolis to regress the development of DM. Further pharmacological in vivo investigations are required to confirm the potent antidiabetic potential of the studied combination.
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Affiliation(s)
- Ahmed A Nada
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt
| | - Aly M Metwally
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt
| | - Aya M Asaad
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt
| | - Ismail Celik
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, 38039, Turkey
| | - Reham S Ibrahim
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt.
| | - Safa M Shams Eldin
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alkhartoom Square, Alexandria, 21521, Egypt
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19
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Yazıcı D, Demir SÇ, Sezer H. Insulin Resistance, Obesity, and Lipotoxicity. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:391-430. [PMID: 39287860 DOI: 10.1007/978-3-031-63657-8_14] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Lipotoxicity, originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas, and muscle. Ectopic lipid accumulation in the kidneys, liver, and heart has important clinical counterparts like diabetic nephropathy in type 2 diabetes mellitus, obesity-related glomerulopathy, nonalcoholic fatty liver disease, and cardiomyopathy. Insulin resistance due to lipotoxicity indirectly lead to reproductive system disorders, like polycystic ovary syndrome. Lipotoxicity has roles in insulin resistance and pancreatic beta-cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway, are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays an important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk, and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.
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Affiliation(s)
- Dilek Yazıcı
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey.
| | - Selin Çakmak Demir
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey
| | - Havva Sezer
- Koç University Medical School, Section of Endocrinology and Metabolism, Koç University Hospital, Topkapi, Istanbul, Turkey
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20
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Singh G, Kumar R, D S D, Chaudhary M, Kaur C, Khurrana N. Thiazolidinedione as a Promising Medicinal Scaffold for the Treatment of Type 2 Diabetes. Curr Diabetes Rev 2024; 20:e201023222411. [PMID: 37867272 DOI: 10.2174/0115733998254798231005095627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 08/13/2023] [Accepted: 08/30/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Thiazolidinediones, also known as glitazones, are considered as biologically active scaffold and a well-established class of anti-diabetic agents for the treatment of type 2 diabetes mellitus. Thiazolidinediones act by reducing insulin resistance through elevated peripheral glucose disposal and glucose production. These molecules activate peroxisome proliferated activated receptor (PPARγ), one of the sub-types of PPARs, and a diverse group of its hybrid have also shown numerous therapeutic activities along with antidiabetic activity. OBJECTIVE The objective of this review was to collect and summarize the research related to the medicinal potential, structure-activity relationship and safety aspects of thiazolidinedione analogues designed and investigated in type 2 diabetes during the last two decades. METHODS The mentioned objective was achieved by collecting and reviewing the research manuscripts, review articles, and patents from PubMed, Science Direct, Embase, google scholar and journals related to the topic from different publishers like Wiley, Springer, Elsevier, Taylor and Francis, Indian and International government patent sites etc. Results: The thiazolidinedione scaffold has been a focus of research in the design and synthesis of novel derivatives for the management of type 2 diabetes, specifically in the case of insulin resistance. The complications like fluid retention, idiosyncratic hepatotoxicity, weight gain and congestive heart failure in the case of trosiglitazone, and pioglitazone have restricted their use. The newer analogues have been synthesized by different research groups to attain better efficacy and less side effects. CONCLUSION Thus, the potential of thiazolidinediones in terms of their chemical evolution, action on nuclear receptors, aldose reductase and free fatty acid receptor 1 is well established. The newer TZD analogues with better safety profiles and tolerability will soon be available in the market for common use without further delay.
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Affiliation(s)
- Gurvinder Singh
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
| | - Rajesh Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
| | - Desna D S
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
| | - Manish Chaudhary
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
| | - Charanjit Kaur
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
| | - Navneet Khurrana
- School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India
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21
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Canto-Cetina T, Silva-Nicanor D, Coral-Vázquez RM, Cano-Martínez LJ, Canto P. RS3480 Polymorphism of FNDC5/Irisin Is Associated with Type 2 Diabetes Mellitus in Maya-Mestizo Women. Metab Syndr Relat Disord 2023; 21:503-508. [PMID: 37566466 DOI: 10.1089/met.2023.0042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2023] Open
Abstract
Objective: To investigate the possible association between rs3480 and rs16835198 of the fibronectin type III domain containing 5 (FNDC5)/Irisin and their haplotypes with the presence of type 2 diabetes mellitus (T2DM) in Maya-Mestizo women. Methods: We studied 547 postmenopausal women of Maya-Mestizo origin. The diagnosis of T2DM was based on the criteria of the American Diabetes Association. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time polymerase chain reaction allelic discrimination. Deviations from Hardy-Weinberg equilibrium and alleles differences, as well as genotype frequencies between groups, were assessed by χ2 tests. Using logistic regression analysis, the odds ratio and 95% confidence intervals were calculated to estimate the association between both polymorphisms of FNDC5/Irisin and the presence of T2DM. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. Results: We found that the G-allele of rs3480, as well as under a dominant model, this polymorphism was significantly associated with T2DM (P = 0.028 and P = 0.003, respectively). Besides, one haplotype was associated with T2DM (P = 0.035). Conclusions: Our results suggest that the FNDC5/Irisin rs3480, and one haplotype formed by rs3480 and rs16835198 were associated with the risk of presenting T2DM in Maya-Mestizo women.
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Affiliation(s)
- Thelma Canto-Cetina
- Laboratorio de Biología de la Reproducción, Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatán, Mérida, México
| | - Diana Silva-Nicanor
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
| | - Ramón Mauricio Coral-Vázquez
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
- Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre," Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Luis Javier Cano-Martínez
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
- Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre," Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
| | - Patricia Canto
- Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de Ciudad de México, Ciudad de México, México
- Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Ciudad de México, México
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22
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Kitamoto T, Accili D. Unraveling the mysteries of hepatic insulin signaling: deconvoluting the nuclear targets of insulin. Endocr J 2023; 70:851-866. [PMID: 37245960 DOI: 10.1507/endocrj.ej23-0150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/30/2023] Open
Abstract
Over 100 years have passed since insulin was first administered to a diabetic patient. Since then great strides have been made in diabetes research. It has determined where insulin is secreted from, which organs it acts on, how it is transferred into the cell and is delivered to the nucleus, how it orchestrates the expression pattern of the genes, and how it works with each organ to maintain systemic metabolism. Any breakdown in this system leads to diabetes. Thanks to the numerous researchers who have dedicated their lives to cure diabetes, we now know that there are three major organs where insulin acts to maintain glucose/lipid metabolism: the liver, muscles, and fat. The failure of insulin action on these organs, such as insulin resistance, result in hyperglycemia and/or dyslipidemia. The primary trigger of this condition and its association among these tissues still remain to be uncovered. Among the major organs, the liver finely tunes the glucose/lipid metabolism to maintain metabolic flexibility, and plays a crucial role in glucose/lipid abnormality due to insulin resistance. Insulin resistance disrupts this tuning, and selective insulin resistance arises. The glucose metabolism loses its sensitivity to insulin, while the lipid metabolism maintains it. The clarification of its mechanism is warranted to reverse the metabolic abnormalities due to insulin resistance. This review will provide a brief historical review for the progress of the pathophysiology of diabetes since the discovery of insulin, followed by a review of the current research clarifying our understanding of selective insulin resistance.
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Affiliation(s)
- Takumi Kitamoto
- Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba 260-8670, Japan
| | - Domenico Accili
- Department of Medicine and Naomi Berrie Diabetes Center, Vagelos College of Physicians and Surgeons of Columbia University, New York, NY 10032 USA
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23
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Vemuri K, Radi SH, Sladek FM, Verzi MP. Multiple roles and regulatory mechanisms of the transcription factor HNF4 in the intestine. Front Endocrinol (Lausanne) 2023; 14:1232569. [PMID: 37635981 PMCID: PMC10450339 DOI: 10.3389/fendo.2023.1232569] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/24/2023] [Indexed: 08/29/2023] Open
Abstract
Hepatocyte nuclear factor 4-alpha (HNF4α) drives a complex array of transcriptional programs across multiple organs. Beyond its previously documented function in the liver, HNF4α has crucial roles in the kidney, intestine, and pancreas. In the intestine, a multitude of functions have been attributed to HNF4 and its accessory transcription factors, including but not limited to, intestinal maturation, differentiation, regeneration, and stem cell renewal. Functional redundancy between HNF4α and its intestine-restricted paralog HNF4γ, and co-regulation with other transcription factors drive these functions. Dysregulated expression of HNF4 results in a wide range of disease manifestations, including the development of a chronic inflammatory state in the intestine. In this review, we focus on the multiple molecular mechanisms of HNF4 in the intestine and explore translational opportunities. We aim to introduce new perspectives in understanding intestinal genetics and the complexity of gastrointestinal disorders through the lens of HNF4 transcription factors.
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Affiliation(s)
- Kiranmayi Vemuri
- Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, United States
- Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
| | - Sarah H. Radi
- Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, United States
- Department of Biochemistry, University of California, Riverside, Riverside, CA, United States
| | - Frances M. Sladek
- Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, United States
| | - Michael P. Verzi
- Department of Genetics, Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, United States
- Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States
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24
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Yoo J, Park JE, Han JS. HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice. Nutrients 2023; 15:2023. [PMID: 37432173 DOI: 10.3390/nu15092023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 04/14/2023] [Accepted: 04/21/2023] [Indexed: 07/12/2023] Open
Abstract
Type 2 diabetes is a disease characterized by hyperglycemia and is a growing health problem worldwide. Since many known diabetes drugs are side effects, it is necessary to develop natural substances with guaranteed safety. HM-chromanone isolated from Portulaca oleracea L. is a homoisoflavonoid compound. We investigated the effects of HM-chromanone on hyperglycemia and its mechanism in C57BL/6J ob/ob mice. C57BL/6J-Jms Slc mice were used as the control group, and C57BL/6J-ob/ob mice were divided into three groups: ob/ob (control), metformin (Met; positive control), and HM-chromanone (HMC). Fasting blood glucose was lower in the HMC group than those in the ob/ob group. Insulin resistance was improved by reducing HbA1c, plasma insulin, and HOMA-IR levels in the HMC group. HMC administration decreased the phosphorylation of IRS-1ser307 and increased the phosphorylation of IRS-1tyr612, PI3K, phosphorylation of AKTser473, and PM-GLUT4 in the skeletal muscles of ob/ob mice, indicating improved insulin signaling. HMC administration also increased the phosphorylation of FOXO1 in the liver of ob/ob mice. This inhibited PEPCK and G6pase involved in gluconeogenesis and regulated phosphorylation of glycogen synthase kinase 3β and glycogen synthase involved in glycogen synthesis. In conclusion, HM-chromanone ameliorates hyperglycemia by PI3K/AKT and improves the FOXO1 in ob/ob mice.
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Affiliation(s)
- Jeong Yoo
- Department of Food Science and Nutrition, Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea
| | - Jae Eun Park
- Department of Food Science and Nutrition, Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea
| | - Ji Sook Han
- Department of Food Science and Nutrition, Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea
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25
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Egu SA, Ali I, Khan KM, Chigurupati S, Qureshi U, Salar U, Taha M, Felemban SG, Venugopal V, Ul-Haq Z. Syntheses, in vitro, and in silico studies of rhodanine-based schiff bases as potential α-amylase inhibitors and radicals (DPPH and ABTS) scavengers. Mol Divers 2023; 27:767-791. [PMID: 35604512 DOI: 10.1007/s11030-022-10454-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 04/27/2022] [Indexed: 10/18/2022]
Abstract
A two-step reaction method was used to synthesize a series of rhodanine-based Schiff bases (2-33) that were characterized using spectroscopic techniques. All compounds were assessed for α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. In comparison to the standard acarbose (IC50 = 9.08 ± 0.07 µM), all compounds demonstrated good to moderate α-amylase inhibitory activity (IC50 = 10.91 ± 0.08-61.89 ± 0.102 µM). Compounds also demonstrated significantly higher DPPH (IC50 = 10.33 ± 0.02-96.65 ± 0.03 µM) and ABTS (IC50 = 12.01 ± 0.12-97.47 ± 0.13 µM) radical scavenging activities than ascorbic acid (DPPH, IC50 = 15.08 ± 0.03 µM; ABTS, IC50 = 16.09 ± 0.17 µM). The limited structure-activity relationship (SAR) suggests that the position and nature of the substituted groups on the phenyl ring have a vital role in varying inhibitory potential. Among the series, compounds with an electron-withdrawing group at the para position showed the highest potency. Kinetic studies revealed that the compounds followed a competitive mode of inhibition. Molecular docking results are found to agree with experimental findings, showing that compounds reside in the active pocket due to the main rhodanine moiety.
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Affiliation(s)
- Samuel Attah Egu
- Department of Pure and Industrial Chemistry, Kogi State University, Anyigba, Kogi, Nigeria
| | - Irfan Ali
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Khalid Mohammed Khan
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
- Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
| | - Sridevi Chigurupati
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 52571, Kingdom of Saudi Arabia
| | - Urooj Qureshi
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Uzma Salar
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
| | - Muhammad Taha
- Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia
| | - Shatha Ghazi Felemban
- Department of Medical Laboratory Science, Fakeeh College for Medical Sciences, Jeddah, Kingdom of Saudi Arabia
| | - Vijayan Venugopal
- Faculty of Pharmacy, AIMST University, 08100, Bedong, Kedah, Malaysia
| | - Zaheer Ul-Haq
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
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Di Giuseppe G, Ciccarelli G, Soldovieri L, Capece U, Cefalo CMA, Moffa S, Nista EC, Brunetti M, Cinti F, Gasbarrini A, Pontecorvi A, Giaccari A, Mezza T. First-phase insulin secretion: can its evaluation direct therapeutic approaches? Trends Endocrinol Metab 2023; 34:216-230. [PMID: 36858875 DOI: 10.1016/j.tem.2023.02.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/26/2023] [Accepted: 02/01/2023] [Indexed: 03/03/2023]
Abstract
Our work is aimed at unraveling the role of the first-phase insulin secretion in the natural history of type 2 diabetes mellitus (T2DM) and its interrelationship with insulin resistance and with β cell function and mass. Starting from pathophysiology, we investigate the impact of impaired secretion on glucose homeostasis and explore postmeal hyperglycemia as the main clinical feature, underlining its relevance in the management of the disease. We also review dietary and pharmacological approaches aimed at improving early secretory defects and restoring residual β cell function. Furthermore, we discuss possible approaches to detect early secretory defects in clinical practice. By providing a journey through human and animal data, we attempt a unification of the recent evidence in an effort to offer a new outlook on β cell secretion.
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Affiliation(s)
- Gianfranco Di Giuseppe
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Gea Ciccarelli
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Laura Soldovieri
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Umberto Capece
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Chiara M A Cefalo
- Department of Clinical and Molecular Medicine, University of Rome - Sapienza, Rome, Italy
| | - Simona Moffa
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Enrico C Nista
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Michela Brunetti
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Cinti
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Alfredo Pontecorvi
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Andrea Giaccari
- Endocrinologia e Diabetologia, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Teresa Mezza
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
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Alarfaj RM, Alayed D. Knowledge and Practice of Use of Insulin Therapy Among Patients With Type 2 Diabetes Attending Primary Health Care Centers, Riyadh, Saudi Arabia: A Cross-Sectional Study. Cureus 2023; 15:e35486. [PMID: 37007415 PMCID: PMC10057695 DOI: 10.7759/cureus.35486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2023] [Indexed: 02/27/2023] Open
Abstract
OBJECTIVE The objective of this study was to explore the level of knowledge and practice of insulin therapy among patients with type 2 diabetes in Saudi Arabia. MATERIALS AND METHODS In this cross-sectional study, 400 pretested structured questionnaires were administered through an interview with patients in a primary health care center. Responses from 324 participants (81% response rate) were analyzed. The questionnaire comprised three main sections: sociodemographic data, a knowledge assessment, and a practice assessment. The total knowledge score was calculated out of 10: 7-10 was excellent, 5.5-6.9 was satisfactory, and less than 5.5 was poor. RESULT Approximately 57% of the participants were ≤ 59 years old, and 56.3% were females. The mean knowledge score was 6.5 (+/-1.6). Participants showed an overall good practice, with 92.5 rotating the site of injection, 83.3% sterilizing the site, and 95.7% taking insulin regularly. The knowledge level was influenced effectively by gender, marital status, educational level, job, frequency of follow-up, having visited a diabetic educator, duration of insulin therapy, and experiencing a hypoglycemic event (p-value <0.05). Knowledge was revealed to significantly influence self-insulin administration, meal-skipping after taking insulin, use of home glucose monitoring, keeping snacks nearby, and taking insulin in relation to meals (p-value <0.05). In some of the practice parameters, patients with high knowledge scores had better practice. CONCLUSION Knowledge of patients with type 2 diabetes mellitus was satisfactory, with significant differences in knowledge according to gender, marital status, educational level, occupation, duration of diabetes, frequency of follow-up, visiting a diabetic educator, and having an experience of the hypoglycemic episode. Participants showed overall good practice, with better practice being associated with a higher knowledge score.
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Lakshminarayana L, Veeraraghavan V, Gouthami K, Srihari R, Chowdadenahalli Nagaraja P. Effect of Abutilon indicum (L) Extract on Adipogenesis, Lipolysis and Cholesterol Esterase in 3T3-L1 Adipocyte Cell Lines. Indian J Clin Biochem 2023; 38:22-32. [PMID: 36684487 PMCID: PMC9852410 DOI: 10.1007/s12291-022-01022-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 01/06/2022] [Indexed: 01/25/2023]
Abstract
Abutilon indicum (L) is an Indian traditional plant used for the treatment of diabetes and heart diseases. The present study is to evaluate the functional of A. indicum leaf extract as insulin like character to inhibit lipolysis and stimulates Adipogenesis activity. The ability of the A. indicum leaf extract in anti-obesity effect of Adipogenesis, lipolysis and cholesterol esterase functions can be predicted by using 3T3-L1 adipocyte cell lines. Substances were isolated from A. indicum leaves and the double filtered crude sample were used for Adipogenesis, lipolysis and cholesterol esterase activity using 3T3-L1 adipocytes at different concentrations. We used differential media-I, differential media-II and maintenance media (MM1) at concentrations of 20, 40, 60, 80, 100, 200 and 400 µg/mL respectively. In addition to the extract, there is a significance increase in glycerol release (p < 0.001) compared with crude and reference compounds. Cholesterol esterase activity predicts the IC50 = 27.11 µg/mL of orlistat positive control compare with IC50 = 8.158 µg/mL of crude extract. Based on the observation, A. indicum leaf extract can promotes lipolysis and differentiated adipocytes. It is potentially used as adjuvant in the treatment of Type 2 diabetes.
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Affiliation(s)
- Lavanya Lakshminarayana
- Department of Biochemistry, School of Applied Sciences, REVA University, Bangalore, 560064 India
| | - V. Veeraraghavan
- Department of Biochemistry, School of Applied Sciences, REVA University, Bangalore, 560064 India
| | - Kuruvalli Gouthami
- Department of Biochemistry, School of Applied Sciences, REVA University, Bangalore, 560064 India
| | - Renuka Srihari
- Department of Biochemistry, Maharani Lakshmi Ammanni College for Women, Bangalore, 560012 India
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Chávez-Aguilar LA, Ávila-Castro D, Merino-Pasaye LE, Peña-Vélez R. Children With Asparaginase-associated Pancreatitis Present Elevated Levels of Insulin, Total Cholesterol, and HOMA-IR Before Starting Acute Lymphoblastic Leukemia Treatment. J Pediatr Hematol Oncol 2022; 44:342-344. [PMID: 34966097 DOI: 10.1097/mph.0000000000002368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 10/19/2021] [Indexed: 11/26/2022]
Abstract
Asparaginase-associated pancreatitis frequently occurs in children with cancer. It is unknown if other factors can influence the development of pancreatitis. A total of 33 pediatric patients with a confirmed diagnosis of acute lymphoblastic leukemia were included in this study. Before acute lymphoblastic leukemia drug treatment, the metabolic parameters (glucose, insulin, homeostasis model assessment insulin resistance, total cholesterol, triglycerides) and body mass index percentile were compared. Children who had acute pancreatitis had higher levels of insulin, homeostasis model assessment insulin resistance, and total cholesterol, compared with children who did not develop acute pancreatitis. These metabolic alterations could play a role in the development of pancreatitis.
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Affiliation(s)
| | - David Ávila-Castro
- Department of Pediatric Hematology, Centro Médico Nacional 20 de Noviembre, Mexico City
| | - Laura E Merino-Pasaye
- Department of Pediatric Hematology, Centro Médico Nacional 20 de Noviembre, Mexico City
| | - Rubén Peña-Vélez
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital General de Puebla "Dr Eduardo Vázquez N", Puebla, Mexico
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30
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Park SW, Kim DY, Bak GT, Hyun DS, Kim SK. Relation of Dietary n-3 and n-6 Fatty Acid Intakes to Metabolic Syndrome in Middle-Aged People Depending on the Level of HbA1c: A Review of National Health and Nutrition Survey Data from 2014 to 2016. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58081017. [PMID: 36013484 PMCID: PMC9413490 DOI: 10.3390/medicina58081017] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 11/16/2022]
Abstract
Background and Objectives: The relation of dietary n-6 fatty acid to metabolic syndrome has not been examined and clearly defined. To improve health in the general population, this study was to investigate the role of n-3 and n-6 fatty acids in the reduction in metabolic syndrome and to observe changes in the effects of these fatty acids depending on the level of insulin resistance. Materials and Methods: This cross-sectional study utilized national health and nutrition survey data from 2014 to 2016. From the data, a relation of n-3 and n-6 fatty acid intakes to metabolic syndrome and Hemoglobin A1c (HbA1c)’s role in the relation was evaluated and analyzed for 4852 patients between 40 and 64 years old. Intake frequency of 112 nutrition and daily consumption amounts were identified, and intakes of n-3 and n-4 fatty acids were calculated from this data. Metabolic syndrome was determined for each participant using diagnostic standards for the Asian population published by the National Cholesterol Education Program. Results: Among the total 4852 subjects, 1583 (32.6%) had metabolic syndrome; 736 of 1875 (39.3%) males and 847 of 2977 (28.5%) females had the syndrome. In males, when their HbA1c was low (<5.4%), intakes of both n-3 and n-6 fatty acids were related to a 43−63% decreased prevalence of metabolic syndrome with significance, and a similar negative tendency was also observed in females. On the contrary, for both males and females, no statistically significant correlation was present when HbA1c was high. Conclusion: It was considered that consistent and regular dietary intakes of n-3 and n-6 fatty acids may contribute greatly to prevent or treat metabolic syndrome in healthy males with normal insulin sensitivity, but the effect of their dietary intakes was found to be limited in a group with strong insulin resistance. The conclusion of this study presents a valuable reference and knowledge to provide nutritional education to the general population.
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Affiliation(s)
- Seo-Woo Park
- Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea; (S.-W.P.); (D.-Y.K.); (G.-T.B.)
| | - Do-Yeong Kim
- Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea; (S.-W.P.); (D.-Y.K.); (G.-T.B.)
| | - Gyeong-Tae Bak
- Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea; (S.-W.P.); (D.-Y.K.); (G.-T.B.)
| | - Dae-Sung Hyun
- Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea; (S.-W.P.); (D.-Y.K.); (G.-T.B.)
- Institute of Occupational and Environmental Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea
- Correspondence: (D.-S.H.); (S.-K.K.)
| | - Sung-Kyung Kim
- Institute of Occupational and Environmental Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea
- Department of Occupational and Environmental Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Korea
- Correspondence: (D.-S.H.); (S.-K.K.)
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Zhou N, Qi H, Liu J, Zhang G, Liu J, Liu N, Zhu M, Zhao X, Song C, Zhou Z, Gong J, Li R, Bai X, Jin Y, Song Y, Yin Y. Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses. Cell Metab 2022; 34:1023-1041.e8. [PMID: 35675826 DOI: 10.1016/j.cmet.2022.05.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 03/01/2022] [Accepted: 05/16/2022] [Indexed: 11/20/2022]
Abstract
The ovarian-tumor-domain-containing deubiquitinases (OTUDs) block ubiquitin-dependent protein degradation and are involved in diverse signaling pathways. We discovered a rare OTUD3 c.863G>A mutation in a family with an early age of onset of diabetes. This mutation reduces the stability and catalytic activity of OTUD3. We next constructed an experiment with Otud3-/- mice and found that they developed worse obesity, dyslipidemia, and insulin resistance than wild-type mice when challenged with a high-fat diet (HFD). We further found that glucose and fatty acids stimulate CREB-binding-protein-dependent OTUD3 acetylation, promoting its nuclear translocation, where OTUD3 regulates various genes involved in glucose and lipid metabolism and oxidative phosphorylation by stabilizing peroxisome-proliferator-activated receptor delta (PPARδ). Moreover, targeting PPARδ using a specific agonist can partially rescue the phenotype of HFD-fed Otud3-/- mice. We propose that OTUD3 is an important regulator of energy metabolism and that the OTUD3 c.863G>A is associated with obesity and a higher risk of diabetes.
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Affiliation(s)
- Na Zhou
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Hailong Qi
- Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Junjun Liu
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University, Jinan, Shandong 250021, China
| | - Guangze Zhang
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jianping Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
| | - Ning Liu
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Minglu Zhu
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xuyang Zhao
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Chang Song
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Zhe Zhou
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Jingjing Gong
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Ridong Li
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Xinyu Bai
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Yan Jin
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
| | - Yongfeng Song
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Shandong Institute of Endocrine & Metabolic Diseases, Shandong First Medical University, Jinan, Shandong 250021, China; Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China.
| | - Yuxin Yin
- Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China; Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China.
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Multi target interactions of essential oil nanoemulsion of Cinnamomum travancoricum against diabetes mellitus via in vitro, in vivo and in silico approaches. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Sadashiv, Sharma P, Dwivedi S, Tiwari S, Singh PK, Pal A, Kumar S. Micro (mi) RNA and Diabetic Retinopathy. Indian J Clin Biochem 2022; 37:267-274. [PMID: 35873619 PMCID: PMC9300788 DOI: 10.1007/s12291-021-01018-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 11/30/2021] [Indexed: 11/24/2022]
Abstract
Diabetic Retinopathy (DR), a debilitating microvascular complication of diabetes, is one of the leading cause of blindness. However, the pathogenesis of this disease is not fully understood. Few Studies have reported the role of MicroRNA (miRNA), which is deregulated or altered in many diseases. Further, few pathways linked genes which have been suggested to be regulated by miRNAs, may play an important role in the regulation of glucose homeostasis and eventually may contribute to the establishment of DR. However, the roles of microRNAs (miRNAs) in DR are still not very clear. In current review, we explored various findings of scientific database demonstrating the role of miRNA in the progression and development of Diabetic Retinopathy.
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Affiliation(s)
- Sadashiv
- Department of Biochemistry, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh 229405 India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342005 India
| | - Shailendra Dwivedi
- Department of Biochemistry, All India Institute of Medical Sciences, Gorakhpur, Uttar Pradesh 273008 India
| | - Sunita Tiwari
- Department of Physiology, King Gearge’s Medical University, Lucknow, Uttar Pradesh 226003 India
| | - Pankaj Kumar Singh
- Department of Biochemistry, All India Institute of Medical Sciences, Vijaypur, Jammu 184120 India
| | - Amit Pal
- Department of Biochemistry, All India Institute of Medical Sciences, Kalyani, West Bengal 5741245 India
| | - Sandeep Kumar
- Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912 USA
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Archer E, Lavie CJ. Obesity Subtyping: The Etiology, Prevention, and Management of Acquired versus Inherited Obese Phenotypes. Nutrients 2022; 14:2286. [PMID: 35684086 PMCID: PMC9183045 DOI: 10.3390/nu14112286] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/22/2022] [Accepted: 05/27/2022] [Indexed: 02/05/2023] Open
Abstract
The etiology of obesity is complex and idiosyncratic-with inherited, behavioral, and environmental factors determining the age and rate at which excessive adiposity develops. Moreover, the etiologic status of an obese phenotype (how and when it developed initially) strongly influences both the short-term response to intervention and long-term health trajectories. Nevertheless, current management strategies tend to be 'one-size-fits-all' protocols that fail to anticipate the heterogeneity of response generated by the etiologic status of each individual's phenotype. As a result, the efficacy of current lifestyle approaches varies from ineffective and potentially detrimental, to clinically successful; therefore, we posit that effective management strategies necessitate a personalized approach that incorporates the subtyping of obese phenotypes. Research shows that there are two broad etiologic subtypes: 'acquired' and 'inherited'. Acquired obesity denotes the development of excessive adiposity after puberty-and because the genesis of this subtype is behavioral, it is amenable to interventions based on diet and exercise. Conversely, inherited obesity subsumes all forms of excessive adiposity that are present at birth and develop prior to pubescence (pediatric and childhood). As the inherited phenotype is engendered in utero, this subtype has irreversible structural (anatomic) and physiologic (metabolic) perturbations that are not susceptible to intervention. As such, the most realizable outcome for many individuals with an inherited subtype will be a 'fit but fat' phenotype. Given that etiologic subtype strongly influences the effects of intervention and successful health management, the purpose of this 'perspective' article is to provide a concise overview of the differential development of acquired versus inherited obesity and offer insight into subtype-specific management.
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Affiliation(s)
- Edward Archer
- Research & Development, EvolvingFX, LLC., Fort Wayne, IN 46835, USA
| | - Carl J. Lavie
- Department of Cardiovascular Diseases, John Ochsner Heart & Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA 70121, USA;
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PET/MRI-Evaluated Activation of Brown Adipose Tissue via Cold Exposure Impacts Lipid Metabolism. Metabolites 2022; 12:metabo12050456. [PMID: 35629960 PMCID: PMC9145038 DOI: 10.3390/metabo12050456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/12/2022] [Accepted: 05/13/2022] [Indexed: 02/04/2023] Open
Abstract
Although brown adipose tissue (BAT) is considered to play a protective role against obesity and type 2 diabetes, the mechanisms of its activation and associations with clinical parameters are not well described. Male adults underwent a 2 h cold exposure (CE) to activate BAT and, based on the results of PET/MRI performed after the CE, were divided into BAT(+) and BAT(−) groups. During the CE procedure, blood samples were collected and alterations in plasma metabolome in both groups were investigated using LC-MS. Additionally, associations between clinical factors and BAT were examined. Moreover, levels of glucose, insulin, leptin, TNF-α, FGF21, and FABP4 were assessed in serum samples. In the BAT(+) group, levels of LPC(17:0), LPE(20:4), LPE(22:4), LPE(22:6), DHA, linoleic acid, and oleic acid increased during CE, whereas levels of sphinganine-phosphate and sphingosine-1-phosphate decreased. Levels of LPE(O-18:0), 9-HpODE, and oleic acid were elevated, while the level of LPE(20:5) was reduced in BAT(+) compared to BAT(−) subjects. AUCs of LPC(18:2), LPC(O-18:2)/LPC(P-18:1), and SM(d32:2) negatively correlated with BAT. In the BAT(+) group, the concentration of FABP4 during and after CE was decreased compared to the basal level. No alterations were observed in the BAT(−) group. In conclusion, using untargeted metabolomics, we proved that the plasma metabolome is affected by cold-induced BAT activation.
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Skurk T, Bosy-Westphal A, Grünerbel A, Kabisch S, Keuthage W, Kronsbein P, Müssig K, Pfeiffer AFH, Simon MC, Tombek A, Weber KS, Rubin D. Dietary recommendations for persons with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2022; 130:S151-S184. [PMID: 35359013 DOI: 10.1055/a-1624-5095] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Thomas Skurk
- ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany.,Else Kröner-Fresenius-Center for Nutritional Medicine, Technical University of Munich, Freising, Germany
| | - Anja Bosy-Westphal
- Institute for Human Nutrition, Faculty of Agricultural and Nutritional Sciences, Christian-Albrechts-University of Kiel, Kiel, Germany
| | | | - Stefan Kabisch
- German Institute of Human Nutrition Potsdam-Rehbrücke, Potsdam, Germany.,Department of Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.,German Center for Diabetes Research (DZD), Munich, Germany
| | - Winfried Keuthage
- Focus Practice for Diabetes and Nutritional Medicine, Münster, Germany
| | - Peter Kronsbein
- Department of Ecotrophology, Niederrhein University of Applied Sciences, Mönchengladbach Campus, Germany
| | - Karsten Müssig
- Department of Internal Medicine, Gastroenterology and Diabetology, Niels Stensen Hospitals, Franziskus Hospital Harderberg, Georgsmarienhütte, Germany
| | - Andreas F H Pfeiffer
- Department of Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Marie-Christine Simon
- Institute of Nutrition and Food Sciences, Rheinische Friedrich-Wilhelms University, Bonn, Germany
| | | | - Katharina S Weber
- Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany
| | - Diana Rubin
- Vivantes Hospital Spandau, Berlin, Germany.,Vivantes Humboldt Hospital, Berlin, Germany
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Kashyap P, Kumar S, Riar CS, Jindal N, Baniwal P, Guiné RPF, Correia PMR, Mehra R, Kumar H. Recent Advances in Drumstick (Moringa oleifera) Leaves Bioactive Compounds: Composition, Health Benefits, Bioaccessibility, and Dietary Applications. Antioxidants (Basel) 2022; 11:antiox11020402. [PMID: 35204283 PMCID: PMC8869219 DOI: 10.3390/antiox11020402] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/12/2022] [Accepted: 02/13/2022] [Indexed: 01/05/2023] Open
Abstract
Based on the availability of many nutrients, Moringa oleifera tree leaves have been widely employed as nutrients and nutraceuticals in recent years. The leaves contain a small amount of anti-nutritional factors and are abundant in innumerable bioactive compounds. Recently, in several in vivo and in vitro investigations, moringa leaves’ bioactive components and functionality are highlighted. Moringa leaves provide several health advantages, including anti-diabetic, antibacterial, anti-cancer, and anti-inflammatory properties. The high content of phytochemicals, carotenoids, and glucosinolates is responsible for the majority of these activities as reported in the literature. Furthermore, there is growing interest in using moringa as a value-added ingredient in the development of functional foods. Despite substantial study into identifying and measuring these beneficial components from moringa leaves, bioaccessibility and bioavailability studies are lacking. This review emphasizes recent scientific evidence on the dietary and bioactive profiles of moringa leaves, bioavailability, health benefits, and applications in various food products. This study highlights new scientific data on the moringa leaves containing nutrient and bioactive profiles, bioavailability, health benefits, and uses in various food items. Moringa has been extensively used as a health-promoting food additive because of its potent protection against various diseases and the widespread presence of environmental toxins. More research is needed for utilization as well as to study medicinal effects and bioaccesibility of these leaves for development of various drugs and functional foods.
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Affiliation(s)
- Piyush Kashyap
- Department of Food Engineering & Technology, Sant Longowal Institute of Engineering & Technology, Longowal 148106, India; (P.K.); (C.S.R.); (N.J.)
- Department of Food Technology and Nutrition, School of Agriculture Lovely Professional University, Phagwara 144401, India
| | - Shiv Kumar
- Food Science & Technology (Hotel Management), Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala 133207, India
- Correspondence: (S.K.); (R.P.F.G.); (H.K.)
| | - Charanjit Singh Riar
- Department of Food Engineering & Technology, Sant Longowal Institute of Engineering & Technology, Longowal 148106, India; (P.K.); (C.S.R.); (N.J.)
| | - Navdeep Jindal
- Department of Food Engineering & Technology, Sant Longowal Institute of Engineering & Technology, Longowal 148106, India; (P.K.); (C.S.R.); (N.J.)
| | | | - Raquel P. F. Guiné
- CERNAS Research Centre, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal;
- Correspondence: (S.K.); (R.P.F.G.); (H.K.)
| | - Paula M. R. Correia
- CERNAS Research Centre, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal;
| | - Rahul Mehra
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India;
| | - Harish Kumar
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur 303002, India;
- Correspondence: (S.K.); (R.P.F.G.); (H.K.)
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How fullerene derivatives (FDs) act on therapeutically important targets associated with diabetic diseases. Comput Struct Biotechnol J 2022; 20:913-924. [PMID: 35242284 PMCID: PMC8861571 DOI: 10.1016/j.csbj.2022.02.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/09/2022] [Accepted: 02/09/2022] [Indexed: 12/12/2022] Open
Abstract
Five proteins related to diabetic disease were selected from Protein Data Bank. Binding scores were calculated for five proteins with 169 fullerene derivatives. Correlation between drug-like descriptors and binding scores activity was examined. The contribution of descriptors to protein-ligand binding was demonstrated. The QSARs models for prediction of binding scores activity were built. Fullerene derivatives (FDs) belong to a relatively new family of nano-sized organic compounds. They are widely applied in materials science, pharmaceutical industry, and (bio) medicine. This research focused on the study of FDs in terms of their potential inhibitory effect on therapeutic targets associated with diabetic disease, as well as analysis of protein–ligand binding in order to identify the key binding characteristics of FDs. Therapeutic drug compounds when entering the biological system usually inevitably encounter and interact with a vast variety of biomolecules that are responsible for many different functions in organisms. Protein biomolecules are the most important functional components and used in this study as target structures. The structures of proteins [(PDB ID: 1BMQ, 1FM6, 1GPB, 1H5U, 1US0)] belonging to the class of anti-diabetes targets were obtained from the Protein Data Bank (PDB). Protein binding activity data (binding scores) were calculated for the dataset of 169 FDs related to these five proteins. Subsequently, the resulting data were analyzed using various machine learning and cheminformatics methods, including artificial neural network algorithms for variable selection and property prediction. The Quantitative Structure-Activity Relationship (QSAR) models for prediction of binding scores activity were built up according to five Organization for Economic Co-operation and Development (OECD) principles. All the data obtained can provide important information for further potential use of FDs with different functional groups as promising medical antidiabetic agents. Binding scores activity can be used for ranking of FDs in terms of their inhibitory activity (pharmacological properties) and potential toxicity.
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Saleh M, Kim JY, March C, Gebara N, Arslanian S. Youth prediabetes and type 2 diabetes: Risk factors and prevalence of dysglycaemia. Pediatr Obes 2022; 17:e12841. [PMID: 34382374 DOI: 10.1111/ijpo.12841] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 01/14/2023]
Abstract
BACKGROUND The American Diabetes Association recommends risk-based screening for dysglycaemia (prediabetes and type 2 diabetes) in youth with overweight/obesity plus ≥1 risk factor. However, evidence for these recommendations is lacking. OBJECTIVES Examine the association between the number of risk factors and the prevalence of dysglycaemia in youth with overweight/obesity at initial presentation. METHODS In a paediatric obesity registry, youth (>10 and <20 years old, body mass index ≥85th percentile) were categorized into four groups according to number of risk factors (1, 2, 3 and ≥4). Based on oral glucose tolerance test, participants were classified into normal glucose tolerance or dysglycaemia. RESULTS Of 635 youth, 31.5% had prediabetes and 6.1% had type 2 diabetes. The prevalence of dysglycaemia was 23.1% with 1 risk factor and increased to 44.9% with ≥4 risk factors (p = 0.025). Dyslipidaemia, family history of type 2 diabetes and maternal history of gestational diabetes were significantly associated with dysglycaemia. Fasting and 2-h insulin, 2-h glucose increased (all p < 0.0001) and ALT increased (p = 0.001) with increasing risk factors. Insulin sensitivity and β-cell function deteriorated significantly with increasing risk factors. CONCLUSION Screening for dysglycaemia in youth with obesity and any additional risk factor is warranted to target early management.
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Affiliation(s)
- Mohamed Saleh
- Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Joon Young Kim
- Department of Exercise Science, Syracuse University, Syracuse, New York, USA
| | - Christine March
- Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nour Gebara
- Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Pediatric Research in Obesity and Metabolism, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Silva Arslanian
- Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Center for Pediatric Research in Obesity and Metabolism, UPMC-Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Yagi N, Komiya I, Arai K, Oishi M, Fukumoto Y, Shirabe S, Yokoyama H, Yamazaki K, Sugimoto H, Maegawa H, Japan Diabetes Clinical Data Management Study Group (JDDM study group),. Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61). J Diabetes Investig 2022; 13:65-73. [PMID: 34191401 PMCID: PMC8756302 DOI: 10.1111/jdi.13621] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/18/2021] [Accepted: 06/27/2021] [Indexed: 01/12/2023] Open
Abstract
AIMS/INTRODUCTION Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients' BMI levels. MATERIALS AND METHODS OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD-treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI. RESULTS Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase-4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m2 . DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m2 , use of BGs and sodium-glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m2 , they were the third most prescribed OADs for patients with BMI >35 kg/m2 after BGs and sodium-glucose cotransporter 2 inhibitors . CONCLUSIONS DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.
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Affiliation(s)
| | - Ichiro Komiya
- Yagi Medical ClinicOkinawaJapan
- Department of Internal MedicineOkinawa Medical HospitalOkinawaJapan
| | | | | | | | | | | | | | | | - Hiroshi Maegawa
- Department of MedicineShiga University of Medical ScienceShigaJapan
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Han T, Yuan T, Liang X, Chen N, Song J, Zhao X, Weng Y, Hu Y. Sarcopenic Obesity with Normal Body Size May Have Higher Insulin Resistance in Elderly Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2022; 15:1197-1206. [PMID: 35469341 PMCID: PMC9034890 DOI: 10.2147/dmso.s360942] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/08/2022] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Data are limited regarding how body composition is linked to insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). We examined the association between body composition and insulin resistance in elderly T2DM patients. METHODS The cross-sectional study included 488 Chinese elderly patients wth T2DM. Subjects were classified into four groups based on body composition: normal body composition (NBC), low muscle mass alone (LMM), high body fat alone (HBF), both low muscle mass and high body fat (LMMHBF). RESULTS The percentage of subjects with LMMHBF was 14.5% (11.9% in men and 17.7% in women). Homeostasis model assessment of insulin resistance (HOMA2-IR) was higher in the LMMHBF group than in the HBF group (p = 0.045), and was also significantly higher in the LMMHBF or HBF group than in the NBC or LMM group. The HBF group showed the highest body mass index (BMI) of the four groups of different body compositions, and the LMMHBF group showed lower BMI than the HBF group; however, there was no significant difference in BMI or waist to hip ratio (WHR) between the LMMHBF group and the NBC group. The LMMHBF and HBF groups were significantly associated with increased risk of insulin resistance compared to the NBC group, with odds ratios (ORs) of 4.47 [95% confidence interval (CI) 2.06-9.68, p < 0.001] and 1.76 (95% CI 1.02-3.02, p = 0.041) respectively, even after the adjustment for covariates. CONCLUSION In China, though elderly T2DM patients with the body composition of sarcopenic obesity (as defined by coexistence of low muscle mass and high body fat) seemed to have normal body size, they exhibited the most severe degree and the highest risk of insulin resistance.
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Affiliation(s)
- Tingting Han
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Ting Yuan
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Xinyue Liang
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Ningxin Chen
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Jia Song
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Xin Zhao
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Yurong Weng
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
| | - Yaomin Hu
- Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China
- Correspondence: Yaomin Hu, Department of Geriatrics, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 Pujian Road, Shanghai, 200127, People’s Republic of China,Tel +86 02168383815, Email
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Luo F, Shi M, Guo J, Cheng Y, Xu X, Zeng J, Huang S, Huang W, Wei W, Wang Y, Chen R, Ma G. Association between the RETN -420C/G polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis of 23 studies. Front Endocrinol (Lausanne) 2022; 13:1039919. [PMID: 36619567 PMCID: PMC9810749 DOI: 10.3389/fendo.2022.1039919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/28/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research. METHODS PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0. RESULTS A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, pheterogeneity <.001; I 2 = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, pheterogeneity <.001; I 2 = 87.1%; and for the recessive model: OR = 0.96, 95% CI = 0.82-1.12, pheterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; pheterogeneity <.001; I 2 = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; pheterogeneity = .98; I 2 = 0.0%)]. CONCLUSIONS Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results.
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Affiliation(s)
- Fei Luo
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Mingjie Shi
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Junhao Guo
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yisen Cheng
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Xusan Xu
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Jieqing Zeng
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- First College of Clinical Medicine, Guangdong Medical University, Zhanjiang, China
| | - Si Huang
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- First College of Clinical Medicine, Guangdong Medical University, Zhanjiang, China
| | - Weijun Huang
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- First College of Clinical Medicine, Guangdong Medical University, Zhanjiang, China
| | - Wenfeng Wei
- Department of Internal Medicine, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Yajun Wang
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
| | - Riling Chen
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- Department of Hematology-Oncology, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- *Correspondence: Guoda Ma, ; Riling Chen,
| | - Guoda Ma
- Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong, China
- Matenal and Child Research Institute, Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
- *Correspondence: Guoda Ma, ; Riling Chen,
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Takahashi K, Mizukami H, Osonoi S, Takeuchi Y, Kudoh K, Sasaki T, Daimon M, Yagihashi S. Islet microangiopathy and augmented β-cell loss in Japanese non-obese type 2 diabetes patients who died of acute myocardial infarction. J Diabetes Investig 2021; 12:2149-2161. [PMID: 34032392 PMCID: PMC8668063 DOI: 10.1111/jdi.13601] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 05/17/2021] [Accepted: 05/19/2021] [Indexed: 11/30/2022] Open
Abstract
AIMS/INTRODUCTION Islets have microvessels that might develop pathological alterations similar to microangiopathy in type 2 diabetes patients. It remains unclear, however, whether the changes correlate with endocrine cell deficits or whether the presence of macroangiopathy influences the islet microvasculature in Japanese type 2 diabetes patients. In this study, we characterized changes of the islet microvessels and endocrine cells in Japanese non-obese patients with type 2 diabetes who died of acute myocardial infarction (AMI). MATERIALS AND METHODS Clinical profiles and islet pathology were examined for 35 diabetes patients who died of AMI (DM + AMI) and 13 diabetes patients who were free from AMI (DM). A total of 13 age-matched, individuals without diabetes who died of AMI and 16 individuals without diabetes who were free from AMI were also studied. Pancreata were subjected to morphometric evaluation of islets, including microvascular alterations of immunostained sections. RESULTS Body mass index in DM + AMI was comparable to those in DM. Compared with DM, DM + AMI showed greater glycated hemoglobin levels, higher prevalence of renal failure, hypertension, smaller β-cell volume density and greater amyloid area. DM + AMI showed an increased microvascular area and density compared with other groups. There was a significant increase in vascular basement membrane thickness and loss of pericytes in DM and DM + AMI compared with individuals without diabetes in each group, and the extent of thickening was correlated with the amyloid area and occurrence of β-cell loss in DM + AMI. CONCLUSIONS Islet microangiopathy was associated with augmented β-cell loss and amyloid deposition in non-obese Japanese type 2 diabetes patients who died of AMI.
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Affiliation(s)
- Kazuhisa Takahashi
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
- Department of Endocrinology and MetabolismHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Hiroki Mizukami
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Sho Osonoi
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
- Department of Endocrinology and MetabolismHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Yuki Takeuchi
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
- Department of Endocrinology and MetabolismHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Kazuhiro Kudoh
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Takanori Sasaki
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Makoto Daimon
- Department of Endocrinology and MetabolismHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
| | - Soroku Yagihashi
- Department of Pathology and Molecular MedicineHirosaki University Graduate School of MedicineHirosaki, AomoriJapan
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Suleiman N, Alkasem M, Hassoun S, Abdalhakam I, Bettahi I, Mir F, Ramanjaneya M, Jerobin J, Iskandarani A, Samra TA, Chandra P, Skarulis M, Abou-Samra AB. Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide. BMJ Open Diabetes Res Care 2021; 9:9/2/e002039. [PMID: 34785564 PMCID: PMC8596034 DOI: 10.1136/bmjdrc-2020-002039] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 06/30/2021] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Decreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity in normal apparently healthy subjects and the levels of adiponectin, adipsin and inflammatory markers. RESEARCH DESIGN AND METHODS A total of 60 participants (aged 18-45, body mass index <28) with a normal oral glucose tolerance test (OGTT) completed hyperinsulinemic-euglycemic clamp (40 mU/m2/min) and body composition test by dual-energy X-ray absorptiometry scan. Blood samples were assayed for glucose, insulin, C peptide, inflammatory markers, oxidative stress markers, adiponectin and adipsin. RESULTS The subjects showed wide variations in the whole-body glucose disposal rate (M value) from 2 to 20 mg/kg/min and were divided into three groups: most responsive (M>12 mg/kg/min, n=17), least responsive (M≤6 mg/kg/min, n=14) and intermediate responsive (M=6.1-12 mg/kg/min, n=29). Insulin and C peptide responses to OGTT were highest among the least insulin sensitive group. Triglycerides, cholesterol, alanine transaminase (ALT) and albumin levels were higher in the least responsive group compared with the other groups. Among the inflammatory markers, C reactive protein (CRP) was highest in the least sensitivity group compared with the other groups; however, there were no differences in the level of soluble receptor for advanced glycation end products and Tumor Necrosis Factor Receptor Superfamily 1B (TNFRS1B). Plasma levels of insulin sensitivity markers, adiponectin and adipsin, and oxidative stress markers, oxidized low-density lipoprotein, total antioxidant capacity and glutathione peroxidase 1, were similar between the groups. CONCLUSIONS A wide range in insulin sensitivity and significant differences in triglycerides, cholesterol, ALT and CRP concentrations were observed despite the fact that the study subjects were homogenous in terms of age, gender and ethnic background, and all had normal screening comprehensive chemistry and normal glucose response to OGTT. The striking differences in insulin sensitivity reflect differences in genetic predisposition and/or environmental exposure. The low insulin sensitivity status associated with increased insulin level may represent an early stage of metabolic abnormality.
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Affiliation(s)
- Noor Suleiman
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | - Meis Alkasem
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | - Shaimaa Hassoun
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
| | | | - Ilham Bettahi
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Fayaz Mir
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Manjunath Ramanjaneya
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Jayakumar Jerobin
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Ahmad Iskandarani
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Tareq A Samra
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Prem Chandra
- Medical Research Center, Hamad Medical Corporation, Doha, Qatar
| | - Monica Skarulis
- Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar
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Skurk T, Bosy-Westphal A, Grünerbel A, Kabisch S, Keuthage W, Kronsbein P, Müssig K, Pfeiffer AFH, Simon MC, Tombek A, Weber KS, Rubin D, für den Ausschuss Ernährung der DDG. Empfehlungen zur Ernährung von Personen mit Typ-2-Diabetes mellitus. DIABETOL STOFFWECHS 2021. [DOI: 10.1055/a-1543-1293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Thomas Skurk
- ZIEL- Institute for Food & Health, Technische Universität München, Freising
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Technische Universität München, Freising
| | - Anja Bosy-Westphal
- Institut für Humanernährung, Agrar- und Ernährungswissenschaftliche Fakultät, Christian-Albrechts-Universität zu Kiel, Kiel
| | | | - Stefan Kabisch
- Abt. Endokrinologie, Diabetes und Ernährungsmedizin, Charité Universitätsmedizin Berlin, Berlin
- Deutsche Zentrum für Diabetesforschung (DZD), München
| | | | - Peter Kronsbein
- Fachbereich Oecotrophologie, Hochschule Niederrhein, Campus Mönchengladbach
| | - Karsten Müssig
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Franziskus-Hospital Harderberg, Georgsmarienhütte
| | - Andreas F. H. Pfeiffer
- Abt. Endokrinologie, Diabetes und Ernährungsmedizin, Charité Universitätsmedizin Berlin, Berlin
| | - Marie-Christine Simon
- Institut für Ernährungs- und Lebensmittelwissenschaften, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn
| | | | - Katharina S. Weber
- Institut für Epidemiologie, Christian-Albrechts-Universität zu Kiel, Kiel
| | - Diana Rubin
- Vivantes Klinikum Spandau, Berlin
- Vivantes Humboldt Klinikum, Berlin
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Gao Y, Li X, Huang Y, Chen J, Qiu M. Bitter Melon and Diabetes Mellitus. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1923733] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Ya Gao
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China
- University of the Chinese Academy of Sciences, Beijing, PR China
- Yunnan Key Laboratory of Natural Medicinal Chemistry, Chinese Academy of Sciences, Kunming, PR China
| | - Xian Li
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China
- University of the Chinese Academy of Sciences, Beijing, PR China
- Yunnan Key Laboratory of Natural Medicinal Chemistry, Chinese Academy of Sciences, Kunming, PR China
| | - Yanjie Huang
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China
- University of the Chinese Academy of Sciences, Beijing, PR China
- Yunnan Key Laboratory of Natural Medicinal Chemistry, Chinese Academy of Sciences, Kunming, PR China
| | - Jianchao Chen
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China
| | - Minghua Qiu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, PR China
- University of the Chinese Academy of Sciences, Beijing, PR China
- Yunnan Key Laboratory of Natural Medicinal Chemistry, Chinese Academy of Sciences, Kunming, PR China
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Pompa M, Panunzi S, Borri A, De Gaetano A. A comparison among three maximal mathematical models of the glucose-insulin system. PLoS One 2021; 16:e0257789. [PMID: 34570804 PMCID: PMC8476045 DOI: 10.1371/journal.pone.0257789] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 09/13/2021] [Indexed: 11/24/2022] Open
Abstract
The most well-known and widely used mathematical representations of the physiology of a diabetic individual are the Sorensen and Hovorka models as well as the UVAPadova Simulator. While the Hovorka model and the UVAPadova Simulator only describe the glucose metabolism of a subject with type 1 diabetes, the Sorensen model was formulated to simulate the behaviour of both normal and diabetic individuals. The UVAPadova model is the most known model, accepted by the FDA, with a high level of complexity. The Hovorka model is the simplest of the three models, well documented and used primarily for the development of control algorithms. The Sorensen model is the most complete, even though some modifications were required both to the model equations (adding useful compartments for modelling subcutaneous insulin delivery) and to the parameter values. In the present work several simulated experiments, such as IVGTTs and OGTTs, were used as tools to compare the three formulations in order to establish to what extent increasing complexity translates into richer and more correct physiological behaviour. All the equations and parameters used for carrying out the simulations are provided.
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Affiliation(s)
- Marcello Pompa
- CNR-IASI, Laboratorio di Biomatematica, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Rome, Italy
- Università Cattolica del Sacro Cuore Rome, Rome, Italy
| | - Simona Panunzi
- CNR-IASI, Laboratorio di Biomatematica, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Rome, Italy
| | - Alessandro Borri
- CNR-IASI, Laboratorio di Biomatematica, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Rome, Italy
| | - Andrea De Gaetano
- CNR-IASI, Laboratorio di Biomatematica, Consiglio Nazionale delle Ricerche, Istituto di Analisi dei Sistemi ed Informatica, Rome, Italy
- CNR-IRIB, Consiglio Nazionale delle Ricerche, Istituto per la Ricerca e l’Innovazione Biomedica Palermo, Palermo, Italy
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Mizukami H, Kudoh K. Diversity of pathophysiology in type 2 diabetes shown by islet pathology. J Diabetes Investig 2021; 13:6-13. [PMID: 34562302 PMCID: PMC8756316 DOI: 10.1111/jdi.13679] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 09/19/2021] [Indexed: 12/18/2022] Open
Abstract
The etiology of type 2 diabetes is multifactorial, in which environmental and genetic factors are involved to varying degrees. This suggests that its pathophysiology might vary depending on the individuals. Knowledge of the differences is critical, because these differences are directly linked to the care and treatment of the patients. Recent studies have attempted to carry out subclassifications of type 2 diabetes based on clinical and genetic differences. However, there is no pathological evidence to support these subclassifications. The pathophysiology of type 2 diabetes is generally divided into insulin resistance in peripheral tissues and pancreatic islet dysfunction. Among them, islet dysfunction causes a deficit in insulin secretion from β-cells. In particular, a deficit in insulin secretion is ascribed to a combination of disruption of the insulin secretory machinery and a decrease in β-cell volume in type 2 diabetes. Recent research has suggested that transdifferentiation and dedifferentiation are involved in the decrease in β-cell volume, and that it might change dynamically depending on the glucose metabolic state. However, it is possible that the numbers of islet cells are decreased in type 2 diabetes. In particular, the loss of endocrine cells due to islet amyloid deposits is an important pathological change in type 2 diabetes in humans. These results show that pathological changes of the islets can be different in each individuals with type 2 diabetes and reflect each pathophysiology, which is useful in establishing further subclassifications and developing tailor-made therapies for type 2 diabetes.
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Affiliation(s)
- Hiroki Mizukami
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kazuhiro Kudoh
- Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Narjis M, Noreen M, Safi SZ, Ilahi NE, Alomar SY, Alkhuriji AF. Cross talk between complete blood count and progression of type II diabetes mellitus. JOURNAL OF KING SAUD UNIVERSITY - SCIENCE 2021; 33:101492. [DOI: 10.1016/j.jksus.2021.101492] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/07/2024]
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Manaithiya A, Alam O, Sharma V, Javed Naim M, Mittal S, Khan IA. GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus. Bioorg Chem 2021; 113:104998. [PMID: 34048996 DOI: 10.1016/j.bioorg.2021.104998] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/05/2021] [Accepted: 05/17/2021] [Indexed: 02/07/2023]
Abstract
Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in β-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependent insulin secretion and glucose-dependent insulinotropic peptide (GIP). In this manuscript, we have reviewed the work done in the last five years (2015-2020) which gives an approach to design, synthesize, evaluate and study the structural activity relationship of novel GPR119 agonist-based lead compounds. Our article would help the researchers and guide their endeavours in the direction of strategy and development of innovative, effective GPR119 agonist-based compounds for the management of diabetes mellitus type 2.
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Affiliation(s)
- Ajay Manaithiya
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Ozair Alam
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India.
| | - Vrinda Sharma
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Mohd Javed Naim
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Shruti Mittal
- Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India
| | - Imran A Khan
- Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi-110062, India
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