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Begzati A, Godinez-Macias KP, Long T, Watrous JD, Moranchel R, Kantz ED, Tuomilehto J, Havulinna AS, Niiranen TJ, Jousilahti P, Salomaa V, Yu B, Norby F, Rebholz CM, Selvin E, Winzeler EA, Cheng S, Alotaibi M, Goyal R, Ideker T, Jain M, Majithia AR. Plasma Lipid Metabolites, Clinical Glycemic Predictors, and Incident Type 2 Diabetes. Diabetes Care 2025; 48:473-480. [PMID: 39761415 PMCID: PMC11870283 DOI: 10.2337/dc24-2266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 12/12/2024] [Indexed: 03/03/2025]
Abstract
OBJECTIVE Plasma metabolite profiling has uncovered several nonglycemic markers of incident type 2 diabetes (T2D). We investigated whether such biomarkers provide information about specific aspects of T2D etiology, such as impaired fasting glucose and impaired glucose tolerance, and whether their association with T2D risk varies by race. RESEARCH DESIGN AND METHODS Untargeted plasma metabolite profiling was performed of participants in the FINRISK 2002 cohort (n = 7,564). Cox regression modeling was conducted to identify metabolites associated with incident T2D during 14 years of follow-up. Metabolites were clustered into pathways using Gaussian graphical modeling. Clusters enriched for T2D biomarkers were further examined for covariation with fasting plasma glucose (FPG), 2-h postchallenge plasma glucose (2hPG), HbA1c, or fasting insulin. Validation analyses and tests of interaction with race were performed in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS Two clusters of metabolites, representing diacylglycerols (DAGs) and phosphatidylcholines (PCs), contained the largest number of metabolite associations with incident T2D. DAGs associated with increased T2D incidence (hazard ratio [HR] 1.22; 95% CI 1.14-1.30) independent of FPG, HbA1c, and fasting insulin, but not 2hPG. PCs were inversely associated with T2D risk (HR 0.78; 95% CI 0.71-0.85) independent of FPG, 2hPG, HbA1c, and fasting insulin. No significant interaction between DAGs or PCs and race was observed. CONCLUSIONS Fasting DAGs may capture information regarding T2D risk similar to that represented by 2hPG; PCs may capture aspects of T2D etiology that differ from those represented by conventional biomarkers. The direction of effect and strength of DAG and PC associations with incident T2D are similar across European and African Americans.
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Affiliation(s)
- Arjana Begzati
- Department of Medicine, University of California San Diego, La Jolla, CA
| | | | - Tao Long
- Department of Medicine, University of California San Diego, La Jolla, CA
- Sapient Bioanalytics, San Diego, CA
| | - Jeramie D. Watrous
- Department of Medicine, University of California San Diego, La Jolla, CA
- Sapient Bioanalytics, San Diego, CA
| | - Rafael Moranchel
- Department of Medicine, University of California San Diego, La Jolla, CA
- Sapient Bioanalytics, San Diego, CA
| | - Edward D. Kantz
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Jaakko Tuomilehto
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Public Health, University of Helsinki, Helsinki, Finland
| | - Aki S. Havulinna
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland
- Department of Computing, University of Turku, Turku, Finland
- Institute for Molecular Medicine Finland, FIMM-HiLIFE, Helsinki, Finland
| | - Teemu J. Niiranen
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland
- Division of Medicine, Turku University Hospital, Turku, Finland
- Department of Internal Medicine, University of Turku, Turku, Finland
| | - Pekka Jousilahti
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Veikko Salomaa
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Bing Yu
- Department of Epidemiology, School of Public Health, University of Texas School of Public Health, Houston, TX
| | - Faye Norby
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN
| | - Casey M. Rebholz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Elizabeth Selvin
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | | | - Susan Cheng
- Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mona Alotaibi
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Ravi Goyal
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Trey Ideker
- Department of Medicine, University of California San Diego, La Jolla, CA
| | - Mohit Jain
- Department of Medicine, University of California San Diego, La Jolla, CA
- Sapient Bioanalytics, San Diego, CA
| | - Amit R. Majithia
- Department of Medicine, University of California San Diego, La Jolla, CA
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Mansouri RA, Aboubakr EM, Alshaibi HF, Ahmed AM. L-arginine administration exacerbates myocardial injury in diabetics via prooxidant and proinflammatory mechanisms along with myocardial structural disruption. World J Diabetes 2025; 16:100395. [PMID: 39959273 PMCID: PMC11718468 DOI: 10.4239/wjd.v16.i2.100395] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/02/2024] [Accepted: 11/25/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND L-arginine (L-Arg) is one of the most widely used amino acids in dietary and pharmacological products. However, the evidence on its usefulness and dose limitations, especially in diabetics is still controversial. AIM To investigate the effects of chronic administration of different doses of L-Arg on the cardiac muscle of type 2 diabetic rats. METHODS Of 96 male rats were divided into 8 groups as follows (n = 12): Control, 0.5 g/kg L-Arg, 1 g/kg L-Arg, 1.5 g/kg L-Arg, diabetic, diabetic + 0.5 g/kg L-Arg, diabetic + 1 g/kg L-Arg, and diabetic + 1.5 g/kg L-Arg; whereas L-Arg was orally administered for 3 months to all treated groups. RESULTS L-Arg produced a moderate upregulation of blood glucose levels to normal rats, but when given to diabetics a significant upregulation was observed, associated with increased nitric oxide, inflammatory cytokines, and malonaldehyde levels in diabetic rats treated with 1 g/kg L-Arg and 1.5 g/kg L-Arg. A substantial decrease in the antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione concentrations, and Nrf-2 tissue depletion were observed at 1 g/kg and 1.5 g/kg L-Arg diabetic treated groups, associated with myocardial injury, fibrosis, α-smooth muscle actin upregulation, and disruption of desmin cardiac myofilaments, and these effects were not noticeable at normal treated groups. On the other hand, L-Arg could significantly improve the lipid profile of diabetic rats and decrease their body weights. CONCLUSION L-Arg dose of 1 g/kg or more can exacerbates the diabetes injurious effects on the myocardium, while 0.5 g/kg dose can improve the lipid profile and decrease the body weight.
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Affiliation(s)
- Rasha A Mansouri
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 22254, Jeddah, Saudi Arabia
- College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Esam M Aboubakr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy-South Valley University, Qena 83523, Egypt
| | - Huda F Alshaibi
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 22254, Jeddah, Saudi Arabia
- Stem Cell Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Adel M Ahmed
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt
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Fotouhi Ardakani A, Anjom-Shoae J, Sadeghi O, Marathe CS, Feinle-Bisset C, Horowitz M. Association between total, animal, and plant protein intake and type 2 diabetes risk in adults: A systematic review and dose-response meta-analysis of prospective cohort studies. Clin Nutr 2024; 43:1941-1955. [PMID: 39032197 DOI: 10.1016/j.clnu.2024.07.001] [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: 12/26/2023] [Revised: 06/04/2024] [Accepted: 07/03/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND AND AIMS While clinical studies indicate that dietary protein may benefit glucose homeostasis in type 2 diabetes (T2D), the impact of dietary protein, including whether the protein is of animal or plant origin, on the risk of T2D is uncertain. We conducted a systematic review and meta-analysis to evaluate the associations of total, animal, and plant protein intakes with the risk of T2D. METHODS A systematic search was performed using multiple data sources, including PubMed/Medline, ISI Web of Science, Scopus, and Google Scholar, with the data cut-off in May 2023. Our selection criteria focused on prospective cohort studies that reported risk estimates for the association between protein intake and T2D risk. For data synthesis, we calculated summary relative risks and 95% confidence intervals for the highest versus lowest categories of protein intake using random-effects models. Furthermore, we conducted both linear and non-linear dose-response analyses to assess the dose-response associations between protein intake and T2D risk. RESULTS Sixteen prospective cohort studies, involving 615,125 participants and 52,342 T2D cases, were identified, of which eleven studies reported data on intake of both animal and plant protein. Intakes of total (pooled effect size: 1.14, 95% CI: 1.04-1.24) and animal (pooled effect size: 1.18, 95% CI: 1.09-1.27) protein were associated with an increased risk of T2D. These effects were dose-related - each 20-g increase in total or animal protein intake increased the risk of T2D by ∼3% and ∼7%, respectively. In contrast, there was no association between intake of plant protein and T2D risk (pooled effect size: 0.98, 95% CI: 0.89-1.08), while replacing animal with plant protein intake (per each 20 g) was associated with a reduced risk of T2D (pooled effect size: 0.80, 95% CI: 0.76-0.84). CONCLUSIONS Our findings indicate that long-term consumption of animal, but not plant, protein is associated with a significant and dose-dependent increase in the risk of T2D, with the implication that replacement of animal with plant protein intake may lower the risk of T2D.
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Affiliation(s)
- Amirmahdi Fotouhi Ardakani
- Student Research Committee, School of Public Health, Kerman University of Medical Sciences, Kerman, Iran; Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Javad Anjom-Shoae
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia
| | - Omid Sadeghi
- Nutrition and Food Security Research Centre and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
| | - Christine Feinle-Bisset
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Sciences to Good Health, University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
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Anjom-Shoae J, Feinle-Bisset C, Horowitz M. Impacts of dietary animal and plant protein on weight and glycemic control in health, obesity and type 2 diabetes: friend or foe? Front Endocrinol (Lausanne) 2024; 15:1412182. [PMID: 39145315 PMCID: PMC11321983 DOI: 10.3389/fendo.2024.1412182] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 07/17/2024] [Indexed: 08/16/2024] Open
Abstract
It is well established that high-protein diets (i.e. ~25-30% of energy intake from protein) provide benefits for achieving weight loss, and subsequent weight maintenance, in individuals with obesity, and improve glycemic control in type 2 diabetes (T2D). These effects may be attributable to the superior satiating property of protein, at least in part, through stimulation of both gastrointestinal (GI) mechanisms by protein, involving GI hormone release and slowing of gastric emptying, as well as post-absorptive mechanisms facilitated by circulating amino acids. In contrast, there is evidence that the beneficial effects of greater protein intake on body weight and glycemia may only be sustained for 6-12 months. While both suboptimal dietary compliance and metabolic adaptation, as well as substantial limitations in the design of longer-term studies are all likely to contribute to this contradiction, the source of dietary protein (i.e. animal vs. plant) has received inappropriately little attention. This issue has been highlighted by outcomes of recent epidemiological studies indicating that long-term consumption of animal-based protein may have adverse effects in relation to the development of obesity and T2D, while plant-based protein showed either protective or neutral effects. This review examines information relating to the effects of dietary protein on appetite, energy intake and postprandial glycemia, and the relevant GI functions, as reported in acute, intermediate- and long-term studies in humans. We also evaluate knowledge relating to the relevance of the dietary protein source, specifically animal or plant, to the prevention, and management, of obesity and T2D.
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Affiliation(s)
- Javad Anjom-Shoae
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
| | - Christine Feinle-Bisset
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
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Benchoula K, Serpell CJ, Mediani A, Albogami A, Misnan NM, Ismail NH, Parhar IS, Ogawa S, Hwa WE. 1H NMR metabolomics insights into comparative diabesity in male and female zebrafish and the antidiabetic activity of DL-limonene. Sci Rep 2024; 14:3823. [PMID: 38360784 PMCID: PMC10869695 DOI: 10.1038/s41598-023-45608-z] [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: 06/13/2023] [Accepted: 10/21/2023] [Indexed: 02/17/2024] Open
Abstract
Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
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Affiliation(s)
- Khaled Benchoula
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
| | | | - Ahmed Mediani
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia
| | - Abdulaziz Albogami
- Biology Department, Faculty of Science, Al-Baha University, 65779-7738, Alaqiq, Saudi Arabia
| | - Norazlan Mohmad Misnan
- Institute for Medical Research Malaysia, No.1, Jalan Setia Murni U13/52, Seksyen U13, Setia Alam, 40170, Shah Alam, Selangor Darul Ehsan, Malaysia
| | - Nor Hadiani Ismail
- Atta-ur-Rahman Institute for Natural Products Discovery, UiTM Puncak Alam Campus, 42300, Puncak Alam, Selangor, Malaysia
| | - Ishwar S Parhar
- Monash University (Malaysia) BRIMS, Jeffrey Cheah School of Medicine and Health Sciences, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
| | - Satoshi Ogawa
- Monash University (Malaysia) BRIMS, Jeffrey Cheah School of Medicine and Health Sciences, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
| | - Wong Eng Hwa
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
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Turek M, Różycka-Sokołowska E, Owsianik K, Bałczewski P. New Perspectives for Antihypertensive Sartans as Components of Co-crystals and Co-amorphous Solids with Improved Properties and Multipurpose Activity. Mol Pharm 2024; 21:18-37. [PMID: 38108281 DOI: 10.1021/acs.molpharmaceut.3c00959] [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: 12/19/2023]
Abstract
Sartans (angiotensin II receptor blockers, ARBs), drugs used in the treatment of hypertension, play a principal role in addressing the global health challenge of hypertension. In the past three years, their potential use has expanded to include the possibility of their application in the treatment of COVID-19 and neurodegenerative diseases (80 clinical studies worldwide). However, their therapeutic efficacy is limited by their poor solubility and bioavailability, prompting the need for innovative approaches to improve their pharmaceutical properties. This review discusses methods of co-crystallization and co-amorphization of sartans with nonpolymeric, low molecular, and stabilizing co-formers, as a promising strategy to synthesize new multipurpose drugs with enhanced pharmaceutical properties. The solid-state forms have demonstrated the potential to address the poor solubility limitations of conventional sartan formulations and offer new opportunities to develop dual-active drugs with broader therapeutic applications. The review includes an in-depth analysis of the co-crystal and co-amorphous forms of sartans, including their properties, possible applications, and the impact of synthetic methods on their pharmacokinetic properties. By shedding light on the solid forms of sartans, this article provides valuable insights into their potential as improved drug formulations. Moreover, this review may serve as a valuable resource for designing similar solid forms of sartans and other drugs, fostering further advances in pharmaceutical research and drug development.
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Affiliation(s)
- Marika Turek
- Institute of Chemistry, Faculty of Science and Technology, Jan Długosz University in Częstochowa, Armii Krajowej 13/15, 42-200 Częstochowa, Poland
| | - Ewa Różycka-Sokołowska
- Institute of Chemistry, Faculty of Science and Technology, Jan Długosz University in Częstochowa, Armii Krajowej 13/15, 42-200 Częstochowa, Poland
| | - Krzysztof Owsianik
- Division of Organic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
| | - Piotr Bałczewski
- Institute of Chemistry, Faculty of Science and Technology, Jan Długosz University in Częstochowa, Armii Krajowej 13/15, 42-200 Częstochowa, Poland
- Division of Organic Chemistry, Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
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Koshovyi O, Vlasova I, Laur H, Kravchenko G, Krasilnikova O, Granica S, Piwowarski JP, Heinämäki J, Raal A. Chemical Composition and Insulin-Resistance Activity of Arginine-Loaded American Cranberry ( Vaccinium macrocarpon Aiton, Ericaceae) Leaf Extracts. Pharmaceutics 2023; 15:2528. [PMID: 38004508 PMCID: PMC10675343 DOI: 10.3390/pharmaceutics15112528] [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: 10/03/2023] [Revised: 10/20/2023] [Accepted: 10/23/2023] [Indexed: 11/26/2023] Open
Abstract
One of the key pathogenetic links in type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside, and quercetin-O-p-coumaroyl hexoside-2 identified by HPLC. In vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under the insulin tolerance test and affected homeostasis model assessment IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide as a carrier gel in semi-solid extrusion 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.
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Affiliation(s)
- Oleh Koshovyi
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia; (O.K.); (J.H.)
- Department of Pharmacognosy, National University of Pharmacy, 53 Pushkinska Str., 61002 Kharkiv, Ukraine (G.K.)
| | - Inna Vlasova
- Department of Pharmacognosy, National University of Pharmacy, 53 Pushkinska Str., 61002 Kharkiv, Ukraine (G.K.)
- Microbiota Lab, Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland (J.P.P.)
| | - Heleriin Laur
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia; (O.K.); (J.H.)
| | - Ganna Kravchenko
- Department of Pharmacognosy, National University of Pharmacy, 53 Pushkinska Str., 61002 Kharkiv, Ukraine (G.K.)
| | - Oksana Krasilnikova
- Department of Pharmacognosy, National University of Pharmacy, 53 Pushkinska Str., 61002 Kharkiv, Ukraine (G.K.)
| | - Sebastian Granica
- Microbiota Lab, Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland (J.P.P.)
| | - Jakub P. Piwowarski
- Microbiota Lab, Department of Pharmaceutical Biology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland (J.P.P.)
| | - Jyrki Heinämäki
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia; (O.K.); (J.H.)
| | - Ain Raal
- Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia; (O.K.); (J.H.)
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Liu Y, Wang H, Liang Y, Guo Z, Qu L, Wang Y, Zhang C, Sun G, Li Y. Dietary intakes of methionine, threonine, lysine, arginine and histidine increased risk of type 2 diabetes in Chinese population: does the mediation effect of obesity exist? BMC Public Health 2023; 23:1551. [PMID: 37582714 PMCID: PMC10428589 DOI: 10.1186/s12889-023-16468-z] [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: 05/15/2023] [Accepted: 08/07/2023] [Indexed: 08/17/2023] Open
Abstract
BACKGROUND Published studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population. METHODS A total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated. RESULTS Higher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid. CONCLUSIONS We found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.
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Affiliation(s)
- Yuyan Liu
- Department of Clinical Epidemiology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Huan Wang
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Yuanhong Liang
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Zijun Guo
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Litong Qu
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Ying Wang
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Chengwen Zhang
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Guifan Sun
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China
- School of Public Health, China Medical University, Shenyang, Liaoning, China
| | - Yongfang Li
- Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, China.
- School of Public Health, China Medical University, Shenyang, Liaoning, China.
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Saka W, Anigbogu C, Kehinde M, Jaja S. L-Arginine supplementation enhanced expression of glucose transporter (GLUT 1) in sickle cell anaemia subjects in the steady state. Curr Res Physiol 2023; 6:100096. [DOI: 10.1016/j.crphys.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 11/05/2022] [Accepted: 11/22/2022] [Indexed: 12/12/2022] Open
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Steviol Glycoside, L-Arginine, and Chromium(III) Supplementation Attenuates Abnormalities in Glucose Metabolism in Streptozotocin-Induced Mildly Diabetic Rats Fed a High-Fat Diet. Pharmaceuticals (Basel) 2022; 15:ph15101200. [PMID: 36297315 PMCID: PMC9607630 DOI: 10.3390/ph15101200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/16/2022] [Accepted: 09/23/2022] [Indexed: 11/24/2022] Open
Abstract
Stevia rebaudiana Bertoni and its glycosides are believed to exhibit several health-promoting properties. Recently, the mechanisms of the anti-diabetic effects of steviol glycosides (SG) have been the subject of intense research. The following study aims to evaluate the results of SG (stevioside (ST) and rebaudioside A (RA)) combined with L-arginine (L-Arg) and chromium(III) (CrIII) supplementation in streptozotocin- (STZ) induced mild type 2 diabetic rats fed a high-fat diet (HFD), with particular emphasis on carbohydrate and lipid metabolisms. The experiment was carried out on 110 male Wistar rats, 100 of which were fed an HFD to induce insulin resistance, followed by an intraperitoneal injection of streptozotocin to induce mild type 2 diabetes. After confirmation of hyperglycemia, the rats were divided into groups. Three groups served as controls: diabetic untreated, diabetic treated with metformin (300 mg/kg BW), and healthy group. Eight groups were fed an HFD enriched with stevioside or rebaudioside A (2500 mg/kg BW) combined with L-arginine (2000 or 4000 mg/kg BW) and Cr(III) (1 or 5 mg/kg BW) for six weeks. The results showed that supplementation with SG (ST and RA) combined with L-arg and Cr(III) could improve blood glucose levels in rats with mild type 2 diabetes. Furthermore, ST was more effective in improving blood glucose levels, insulin resistance indices, and very low-density lipoprotein cholesterol (VLDL-C) concentrations than RA. Although L-arg and Cr(III) supplementation did not independently affect most blood carbohydrate and lipid indices, it further improved some biomarkers when combined, particularly with ST. Notably, the beneficial impact of ST on the homeostatic model assessment–insulin resistance (HOMA-IR) and on the quantitative insulin-sensitivity check index (QUICKI) was strengthened when mixed with a high dose of L-arg, while its impact on antioxidant status was improved when combined with a high dose of Cr(III) in rats with mild type 2 diabetes. In conclusion, these results suggest that supplementary stevioside combined with L-arginine and Cr(III) has therapeutic potential for mild type 2 diabetes. However, further studies are warranted to confirm these effects in other experimental models and humans.
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The Potential of L-Arginine in Prevention and Treatment of Disturbed Carbohydrate and Lipid Metabolism—A Review. Nutrients 2022; 14:nu14050961. [PMID: 35267936 PMCID: PMC8912821 DOI: 10.3390/nu14050961] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/16/2022] [Accepted: 02/22/2022] [Indexed: 01/27/2023] Open
Abstract
L-arginine, an endogenous amino acid, is a safe substance that can be found in food. The compound is involved in synthesis of various products responsible for regulatory functions in the body. Particularly noteworthy is, among others, nitric oxide, a signaling molecule regulating carbohydrate and lipid metabolism. The increasing experimental and clinical data indicate that L-arginine supplementation may be helpful in managing disturbed metabolism in obesity, regulate arterial blood pressure or alleviate type 2 diabetes symptoms, but the mechanisms underlying these effects have not been sufficiently elucidated. This review aims to present the up-to-date information regarding the current uses and health-promoting potential of L-arginine, its effects on nitric oxide, carbohydrate and lipid metabolisms, based on the results of in vivo, in vitro studies, and clinical human trials. Available literature suggests that L-arginine may have beneficial effects on human health. However, some studies found that higher dietary L-arginine is associated with worsening of an existing disease or may be potential risk factor for development of some diseases. The mechanisms of regulatory effects of L-arginine on carbohydrate and lipid metabolism have not been fully understood and are currently under investigation.
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Amperometric Biosensors for L-Arginine Determination Based on L-Arginine Oxidase and Peroxidase-Like Nanozymes. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app11157024] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
There are limited data on amperometric biosensors (ABSs) for L-arginine (Arg) determination based on oxidases that produce hydrogen peroxide (H2O2) as a byproduct of enzymatic reaction, and artificial peroxidases (POs) for decomposition of H2O2. The most frequently proposed Arg-sensitive oxidase-based ABSs contain at least two enzymes in the bioselective layer; this complicates the procedure and increases the cost of analysis. Therefore, the construction of a one-enzyme ABS for Arg analysis is a practical problem. In the current work, fabrication, and characterization of three ABS types for the direct measurement of Arg were proposed. L-arginine oxidase (ArgO) isolated from the mushroom Amanita phalloides was co-immobilized with PO-like nanozymes (NZs) on the surface of graphite electrodes. As PO mimetics, chemically synthesized NZs of CeCu (nCeCU) and NiPtPd (nNiPtPd), as well as green-synthesized hexacyanoferrate of copper (gCuHCF), were used. The novel ABSs exhibited high sensitivity and selectivity to Arg, broad linear ranges and good storage stabilities. Two ABSs were tested on real samples of products containing Arg, including the pharmaceutical preparation “Tivortine”, juices, and wine. A high correlation (R = 0.995) was demonstrated between the results of testing “Tivortine” and juice using nCeCU/GE and nNiPtPd/GE. It is worth mentioning that only a slight difference (less than 1%) was observed for “Tivortin” between the experimentally determined content of Arg and its value declared by the producer. The proposed ArgO-NZ-based ABSs may be promising for Arg analysis in different branches of science, medicine, and industry.
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