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1
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Liao TI, Ho CY, Chin SC, Wang YC, Chan KC, Chen SL. Sequential Impact of Diabetes Mellitus on Deep Neck Infections: Comparison of the Clinical Characteristics of Patients with and without Diabetes Mellitus. Healthcare (Basel) 2024; 12:1383. [PMID: 39057526 PMCID: PMC11276557 DOI: 10.3390/healthcare12141383] [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: 06/01/2024] [Revised: 07/06/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Deep neck infections (DNIs) can compromise the airway and are associated with high morbidity and mortality rates. Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia that is associated with several comorbidities. We compared the clinical characteristics of DNI patients with and without DM. METHODS This study recorded the relevant clinical variables of 383 patients with DNIs between November 2016 and September 2022; of those patients, 147 (38.38%) had DM. The clinical factors between DNI patients with and without DM were assessed. RESULTS Patients with DM were older (p < 0.001), had higher white blood cell counts (p = 0.029) and C-reactive protein levels (CRP, p < 0.001), had a greater number of deep neck spaces (p = 0.002) compared to patients without DM, and had longer hospital stays (p < 0.001). Klebsiella pneumoniae was cultured more frequently from patients with DM than those without DM (p = 0.002). A higher CRP level (OR = 1.0094, 95% CI: 1.0047-1.0142, p < 0.001) was a significant independent risk factor for DM patients with prolonged hospitalization. The lengths of hospital stays in patients with poorly controlled DM were longer than those with well-controlled DM (p = 0.027). CONCLUSIONS DNI disease severity and outcomes were worse in patients with DM than those without DM. Antibiotics effective against Klebsiella pneumoniae should be used for DNI patients with DM. DNI patients with DM and high CRP levels had more prolonged hospitalizations. Appropriate blood glucose control is essential for DNI patients with DM.
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Affiliation(s)
- Ting-I Liao
- School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; (T.-I.L.); (C.-Y.H.); (S.-C.C.); (K.-C.C.)
| | - Chia-Ying Ho
- School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; (T.-I.L.); (C.-Y.H.); (S.-C.C.); (K.-C.C.)
- Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Shy-Chyi Chin
- School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; (T.-I.L.); (C.-Y.H.); (S.-C.C.); (K.-C.C.)
- Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Yu-Chien Wang
- Department of Otorhinolaryngology & Head and Neck Surgery, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan;
- Department of Otorhinolaryngology & Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Kai-Chieh Chan
- School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; (T.-I.L.); (C.-Y.H.); (S.-C.C.); (K.-C.C.)
- Department of Otorhinolaryngology & Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Shih-Lung Chen
- School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; (T.-I.L.); (C.-Y.H.); (S.-C.C.); (K.-C.C.)
- Department of Otorhinolaryngology & Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
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2
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Krause M, De Vito G. Type 1 and Type 2 Diabetes Mellitus: Commonalities, Differences and the Importance of Exercise and Nutrition. Nutrients 2023; 15:4279. [PMID: 37836562 PMCID: PMC10574155 DOI: 10.3390/nu15194279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 09/16/2023] [Indexed: 10/15/2023] Open
Abstract
Diabetes mellitus represents a group of physiological dysfunctions characterized by hyperglycaemia resulting directly from insulin resistance (in the case of type 2 diabetes mellitus-T2DM), inadequate insulin secretion/production, or excessive glucagon secretion (in type 1 diabetes mellitus-T1DM) [...].
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Affiliation(s)
- Maurício Krause
- Laboratório de Inflamação, Metabolismo e Exercício (LAPIMEX) e Laboratório de Fisiologia Celular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil
| | - Giuseppe De Vito
- Neuromuscular Physiology Laboratory, Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy;
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3
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Myokines and Resistance Training: A Narrative Review. Int J Mol Sci 2022; 23:ijms23073501. [PMID: 35408868 PMCID: PMC8998961 DOI: 10.3390/ijms23073501] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 01/27/2023] Open
Abstract
In the last few years, the muscular system has gained attention due to the discovery of the muscle-secretome and its high potency for retaining or regaining health. These cytokines, described as myokines, released by the working muscle, are involved in anti-inflammatory, metabolic and immunological processes. These are able to influence human health in a positive way and are a target of research in metabolic diseases, cancer, neurological diseases, and other non-communicable diseases. Therefore, different types of exercise training were investigated in the last few years to find associations between exercise, myokines and their effects on human health. Particularly, resistance training turned out to be a powerful stimulus to enhance myokine release. As there are different types of resistance training, different myokines are stimulated, depending on the mode of training. This narrative review gives an overview about resistance training and how it can be utilized to stimulate myokine production in order to gain a certain health effect. Finally, the question of why resistance training is an important key regulator in human health will be discussed.
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4
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Wake AD. Protective effects of physical activity against health risks associated with type 1 diabetes: "Health benefits outweigh the risks". World J Diabetes 2022; 13:161-184. [PMID: 35432757 PMCID: PMC8984568 DOI: 10.4239/wjd.v13.i3.161] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/08/2021] [Accepted: 02/20/2022] [Indexed: 02/06/2023] Open
Abstract
The magnitude of diabetes mellitus (DM) has increased in recent decades, where the number of cases and the proportion of the disease have been gradually increasing over the past few decades. The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease. The prevalence of type 1 DM (T1DM) is increasing globally, and it has a very significant burden on countries and at an individual level. T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications. This study aims to discuss the health benefits of physical activity (PA) in T1DM patients. The present review article was performed following a comprehensive literature search. The search was conducted using the following electronic databases: "Cochrane Library", Web of Science, PubMed, HINARI, EMBASE, Google for grey literature, Scopus, African journals Online, and Google Scholar for articles published up to June 21, 2021. The present review focused on the effects of PA on many outcomes such as blood glucose (BG) control, physical fitness, endothelial function, insulin sensitivity, well-being, the body defense system, blood lipid profile, insulin resistance, cardiovascular diseases (CVDs), insulin requirements, blood pressure (BP), and mortality. It was found that many studies recommended the use of PA for the effective management of T1DM. PA is a component of comprehensive lifestyle modifications, which is a significant approach for the management of T1DM. It provides several health benefits, such as improving BG control, physical fitness, endothelial function, insulin sensitivity, well-being, and the body defense system. Besides this, it reduces the blood lipid profile, insulin resistance, CVDs, insulin requirements, BP, and mortality. Overall, PA has significant and essential protective effects against the health risks associated with T1DM. Even though PA has several health benefits for patients with T1DM, these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular. However, several effective strategies have been identified to control exercise-induced hypoglycemia in these patients. Finally, the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. It also provides suggestions for the future direction of research in this field.
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Affiliation(s)
- Addisu Dabi Wake
- Department of Nursing, College of Health Sciences, Arsi University, Asella 193/4, Ethiopia
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5
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Dor-Haim H, Katzburg S, Revach P, Levine H, Barak S. The impact of COVID-19 lockdown on physical activity and weight gain among active adult population in Israel: a cross-sectional study. BMC Public Health 2021; 21:1521. [PMID: 34362319 PMCID: PMC8343341 DOI: 10.1186/s12889-021-11523-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 07/19/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The COVID-19 outbreak holds public health concerns. The stay-at-home increases sedentary behavior, with unintended adverse outcomes. Since organized recreation and sports facilities were closed, we aimed to study how the crisis of closure affected exercise habits and weight gain among the trainee population in Israel. We examined differences in weight gain among individuals with different PA activities and assessed their ability to adapt to digital media as an alternative training structure. METHODS A cross-sectional survey consisted of a multiple-choice questionnaire obtained using a web-based survey application. Trainees (1202) who exercised steadily anonymously answered the questionnaire sent by their coaches regarding their activity and weight gain during lockdown times. RESULTS Results confirmed that 70% of Israelis trained less than their usual routine, 60% used digital media for training, 55% gained weight. Half of the respondents gained more than 2 kg, with an average increase of 1.2 kg. However, those who exhibited a higher physical activity level gained less weight. Using digital media for training was associated with higher physical activity levels. The aged population was less likely to use digital media. CONCLUSIONS Since increased sedentary behavior could increase the risk for potential worsening of health conditions, health agencies should look for strategies, including digital remote media training to promote physical activity and subsequently, preventing the increased burden of future comorbidities worsening by a sedentary lifestyle. Approval: by the Helsinki ethics committee of Sheba Medical Center (6504-19-SMC).
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Affiliation(s)
- Horesh Dor-Haim
- O2 Health Promotion and Sports Medicine Department, The Howard and Mary Edith Cosell Association for Physical Education, the Safra sports center, Hebrew University, Givat Ram, Jerusalem, Israel.
| | - Sara Katzburg
- O2 Health Promotion and Sports Medicine Department, The Howard and Mary Edith Cosell Association for Physical Education, the Safra sports center, Hebrew University, Givat Ram, Jerusalem, Israel
- Department of Developmental Biology and Cancer Research, Israel-Canada Medical Research Institute, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Polla Revach
- O2 Health Promotion and Sports Medicine Department, The Howard and Mary Edith Cosell Association for Physical Education, the Safra sports center, Hebrew University, Givat Ram, Jerusalem, Israel
| | - Hagai Levine
- Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Sharon Barak
- The Edmond and Lily Safra Children's Hospital, Department of Pediatric Rehabilitation, The Chaim Sheba Medical Center, Ramat-Gan, Israel
- Kaye Academic College of Education, Beer-Sheva, Israel
- College of Public Health Ben-Gurion University of the Negev, Beer-Sheva, Israel
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6
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Martha BA, Vacchi CDO, Fattori RA, Macagnan FE. Effect of physical exercise on the functional capacity of children and adolescents submitted to transplantation of hematopoietic stem cells-A systematic review with meta-analysis. J Child Health Care 2021; 25:18-30. [PMID: 32013540 DOI: 10.1177/1367493520903626] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Previous studies have shown beneficial effects of physical exercise (PE) in adults submitted to hematopoietic stem cell transplantation (HSCT). Conduct a systematic review about the effects of PE on the functional capacity of children and adolescents submitted to HSCT. The studies were searched in the databases MEDLINE (via PubMed), Central Register of Controlled Trials (Cochrane CENTRAL), EMBASE, LILACS, and Evidence Database in Physical Therapy (PEDro) (CRD42018080093). Two independent reviewers performed the article selection, data extraction, and methodological quality assessment. Randomized and nonrandomized clinical trials comparing PE with usual treatment in children and adolescents aged 3-18 years were included. The risk of bias was assessed using the Cochrane Collaboration tool and ROBINS-I tool, and the overall quality of the evidence was determined by the GRADE system. We included three studies with 91 patients. PE improved the functional capacity assessed by the timed up and down stairs test (MD -1.23 [95% CI, 2.27 to -.20, I2 = 0%]), but there was no significant effect in the six-minute walk test (MD 44.63 [95% CI, -20.86 to 110.13, I2 = 83%]). The benefits regarding quality of life and peripheral muscle strength of these individuals were not clearly demonstrated, but positive responses were observed in relation to the analyzed data. None of the studies evaluated the fatigue. The limitations found were the high heterogeneity between studies, as well as the sample size and the low methodological rigor. PE might be favorable to improve the functional capacity of children and adolescents treated with HSCT. However, further studies are needed to clarify the best PE program.
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Affiliation(s)
- Bianca Andrade Martha
- Postgraduate Program in Rehabilitation Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
| | - Cindy de Oliveira Vacchi
- Postgraduate Program in Rehabilitation Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
| | - Rafael Ailton Fattori
- Multiprofessional Residency Program in Oncohematology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
| | - Fabrício Edler Macagnan
- Postgraduate Program in Rehabilitation Sciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil.,Multiprofessional Residency Program in Oncohematology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil.,Department of Physiotherapy of the Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil
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7
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Responses to Low- and High-Intensity Exercise in Adolescents with Type 1 Diabetes in Relation to Their Level of VO 2 Max. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18020692. [PMID: 33467392 PMCID: PMC7830455 DOI: 10.3390/ijerph18020692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/31/2020] [Accepted: 01/09/2021] [Indexed: 12/20/2022]
Abstract
The purpose of this study was to investigate the influence of maximal oxygen uptake (VO2 max) on the glycemic changes during low and high intensity exercises in young type 1 diabetic patients. Twenty boys (age: 14.3 ± 1.6 years; height: 171.0 ± 11.3 cm; weight; 59.5 ± 12.8 kg) were divided into low-fit group (LFG, n = 10) and high-fit group (HFG, n = 10). According to the experimental design, participants performed three physical efforts (VO2 max test, mixed aerobic-anaerobic effort and aerobic effort) on the cycloergometer, during which real-time glycemia was measured. Mixed aerobic-anaerobic exercise demanded significantly smaller carbohydrate supplementation (0.2 ± 0.2 g/kg during exercise) than the aerobic test session (0.4 ± 0.3 g/kg during exercise). Moreover, patients with higher VO2 max had lower tendency for glycemic changes during the aerobic effort. The results of the current study suggest that young type 1 diabetic patients should perform different intensity activities using continuous glycemic monitoring system to avoid acute and chronic complications of the disease.
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8
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Jafari-Vayghan H, Varshosaz P, Hajizadeh-Sharafabad F, Razmi HR, Amirpour M, Tavakoli-Rouzbehani OM, Alizadeh M, Maleki V. A comprehensive insight into the effect of glutamine supplementation on metabolic variables in diabetes mellitus: a systematic review. Nutr Metab (Lond) 2020; 17:80. [PMID: 32983244 PMCID: PMC7517657 DOI: 10.1186/s12986-020-00503-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 09/10/2020] [Indexed: 12/14/2022] Open
Abstract
Diabetes mellitus is one of the most important threats to human health in the twenty-first century.
The use of complementary and alternative medicine to prevent, control, and reduce the complications of diabetes mellitus is increasing at present. Glutamine amino acid is known as a functional food.
The purpose of this systematic review is to determine the potential role of glutamine supplementation on metabolic variables in diabetes mellitus. For this review, PubMed, SCOPUS, Embase, ProQuest, and Google Scholar databases were searched from inception through April 2020. All clinical trial and animal studies assessing the effects of glutamine on diabetes mellitus were eligible for inclusion. 19 studies of 1482 articles met the inclusion criteria. Of the 19 studies, nine studies reported a significant increase in serum GLP-1 levels. Also, eight studies showed reducing in serum levels of fasting blood sugar, four studies reducing in postprandial blood sugar, and triglyceride after glutamine supplementation. Although glutamine resulted in a significant increase in insulin production in seven studies, the findings on Hb-A1c levels were inconclusive. In addition to, despite of the results was promising for the effects of glutamine on weight changes, oxidative stress, and inflammation, more precise clinical trials are needed to obtain more accurate results. In conclusion, glutamine supplementation could improve glycemic control and levels of incretins (such as GLP-1 and GIP) in diabetes mellitus. However, more studies are needed for future studies.
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Affiliation(s)
- Hamed Jafari-Vayghan
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.,Faculty of Health, Arak University of Medical Sciences, Arak, Iran
| | - Parisa Varshosaz
- Departments of Chemistry and Biochemistry, and Biology and Biomolecular Sciences Program, Laurentian University, Sudbury, ON Canada
| | - Fatemeh Hajizadeh-Sharafabad
- Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Reza Razmi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Amirpour
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Alizadeh
- Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahid Maleki
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
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9
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Bittencourt A, Schroeder HT, Porto RR, de Lemos Muller CH, Krause M, Homem de Bittencourt PI. Heat shock response to exercise in pancreatic islets of obese mice. Biochimie 2019; 168:28-40. [PMID: 31678111 DOI: 10.1016/j.biochi.2019.10.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/27/2019] [Indexed: 12/18/2022]
Abstract
Chronic obesity imposes an organismal state of low-grade inflammation because the physiological resolution of inflammation is progressively repressed giving rise to cellular senescence and its accompanying Senescence-Associated Secretory Phenotype (SASP), which avoids apoptosis but perpetuates the relay of inflammatory signals from adipose tissue toward the rest of the body. Conversely, resolution of inflammation depends on the integrity of heat shock response (HSR) pathway that leads to the expression of cytoprotective and anti-inflammatory protein chaperones of the 70 kDa family (HSP70). However, chronic exposure to the aforementioned injuring factors leads to SASP, which, in turn, suppresses the HSR. A main metabolic tissue severely jeopardized by obesity-related dysfunctions is the endocrine pancreas, particularly β-cells of the islets of Langerhans. Because exercise is a powerful inducer of HSR and predicted to alleviate negative health outcomes of obesity, we sought whether obesity influence HSP70 expression in pancreatic islets and other metabolic tissues (adipose tissue and skeletal muscle) of adult B6.129SF2/J mice fed on a high-fat diet (HFD) for 13 weeks since the weaning and whether acute exercise as well as moderate-intensity exercise training (8 weeks) could interfere with this scenario. We showed that acute exercise of moderate intensity protects pancreatic islets against cytokine-induced cell death. In addition, acute exercise challenge time-dependently increased islet HSP70 that peaked at 12 h post-exercise in both trained and untrained mice fed on a control diet, suggesting an adequate HSR to exercise training. Unexpectedly, however, neither exercise training nor acute exercise challenges were able to increase islet HSP70 contents in trained mice submitted to HFD, but only in untrained HFD animals. In parallel, HFD disrupted glycemic status which is accompanied by loss of muscular mass resembling sarcopenic obesity that could not be rescued by exercise training. These results suggest that exercise influences HSR in pancreatic islets but obesity undermines islet, muscle and adipose tissue HSR, which is associated with metabolic abnormalities observed in such tissues.
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Affiliation(s)
- Aline Bittencourt
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Helena Trevisan Schroeder
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Rossana Rosa Porto
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Carlos Henrique de Lemos Muller
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Mauricio Krause
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Paulo Ivo Homem de Bittencourt
- Laboratory of Cellular Physiology (FisCel) and Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX), Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
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Bahrami D, Mozaffari-Khosravi H, Zavar-Reza J. The effect of oral L-arginine supplementation on lipid profile, glycemic status, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2019. [DOI: 10.3233/mnm-180233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Affiliation(s)
- Davood Bahrami
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Hassan Mozaffari-Khosravi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Diabetic Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Javad Zavar-Reza
- Department of Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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11
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Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients 2018; 10:nu10111564. [PMID: 30360490 PMCID: PMC6266414 DOI: 10.3390/nu10111564] [Citation(s) in RCA: 642] [Impact Index Per Article: 91.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 10/13/2018] [Accepted: 10/16/2018] [Indexed: 02/07/2023] Open
Abstract
Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it is currently difficult to determine whether glutamine supplementation (oral/enteral or parenteral) should be recommended based on the amino acid plasma/bloodstream concentration (also known as glutaminemia). Although the beneficial immune-based effects of glutamine supplementation are already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review of how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism and action, and important issues related to the effects of glutamine supplementation in catabolic situations.
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Affiliation(s)
- Vinicius Cruzat
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia.
- Faculty of Health, Torrens University, Melbourne 3065, Australia.
| | - Marcelo Macedo Rogero
- Department of Nutrition, Faculty of Public Health, University of São Paulo, Avenida Doutor Arnaldo 715, São Paulo 01246-904, Brazil.
| | - Kevin Noel Keane
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia.
| | - Rui Curi
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo 01506-000, Brazil.
| | - Philip Newsholme
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia.
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12
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Cruzat V, Macedo Rogero M, Noel Keane K, Curi R, Newsholme P. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients 2018. [PMID: 30360490 DOI: 10.20944/preprints201809.0459.v1] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it is currently difficult to determine whether glutamine supplementation (oral/enteral or parenteral) should be recommended based on the amino acid plasma/bloodstream concentration (also known as glutaminemia). Although the beneficial immune-based effects of glutamine supplementation are already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review of how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism and action, and important issues related to the effects of glutamine supplementation in catabolic situations.
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Affiliation(s)
- Vinicius Cruzat
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia. .,Faculty of Health, Torrens University, Melbourne 3065, Australia.
| | - Marcelo Macedo Rogero
- Department of Nutrition, Faculty of Public Health, University of São Paulo, Avenida Doutor Arnaldo 715, São Paulo 01246-904, Brazil.
| | - Kevin Noel Keane
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia.
| | - Rui Curi
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo 01506-000, Brazil.
| | - Philip Newsholme
- School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia.
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Codella R, Terruzzi I, Luzi L. Why should people with type 1 diabetes exercise regularly? Acta Diabetol 2017; 54:615-630. [PMID: 28289908 DOI: 10.1007/s00592-017-0978-x] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Accepted: 02/27/2017] [Indexed: 01/09/2023]
Abstract
Plethoric evidence reminds of the protective effects of exercise against a number of health risks, across all ages, in the general population. The benefits of exercise for individuals with type 2 diabetes are indisputable. An in-depth understanding of energy metabolism has reasonably entailed exercise as a cornerstone in the lifestyle of almost all subjects with type 1 diabetes. Nevertheless, individuals with type 1 diabetes often fail in accomplishing exercise guidelines and they are less active than their peer without diabetes. Two major obstacles are feared by people with type 1 diabetes who wish to exercise regularly: management of blood glucose control and hypoglycemia. Nowadays, strategies, including glucose monitoring technology and insulin pump therapy, have significantly contributed to the participation in regular physical activity, and even in competitive sports, for people with type 1 diabetes. Novel modalities of training, like different intensity, interspersed exercise, are as well promising. The beneficial potential of exercise in type 1 diabetes is multi-faceted, and it has to be fully exploited because it goes beyond the insulin-mimetic action, possibly through immunomodulation.
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Affiliation(s)
- Roberto Codella
- Department of Biomedical Sciences for Health, University of Milan, Via F.lli Cervi 93, Segrate, 20090, Milan, Italy.
| | - Ileana Terruzzi
- Diabetes Research Institute, Metabolism, Nutrigenomics and Cellular Differentiation Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Livio Luzi
- Department of Biomedical Sciences for Health, University of Milan, Via F.lli Cervi 93, Segrate, 20090, Milan, Italy
- Metabolism Research Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy
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Farinha JB, Krause M, Rodrigues-Krause J, Reischak-Oliveira A. Exercise for type 1 diabetes mellitus management: General considerations and new directions. Med Hypotheses 2017; 104:147-153. [DOI: 10.1016/j.mehy.2017.05.033] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/05/2017] [Accepted: 05/28/2017] [Indexed: 12/17/2022]
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Codella R. Boiling factors in the pot of type 1 diabetes mellitus management: the role of exercise. Med Hypotheses 2017; 105:48. [PMID: 28735652 DOI: 10.1016/j.mehy.2017.06.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 06/28/2017] [Indexed: 01/05/2023]
Affiliation(s)
- Roberto Codella
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; Metabolism Research Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
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16
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Heck TG, Scomazzon SP, Nunes PR, Schöler CM, da Silva GS, Bittencourt A, Faccioni-Heuser MC, Krause M, Bazotte RB, Curi R, Homem de Bittencourt PI. Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio. Cell Stress Chaperones 2017; 22:271-291. [PMID: 28251488 PMCID: PMC5352601 DOI: 10.1007/s12192-017-0771-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 01/24/2017] [Accepted: 01/31/2017] [Indexed: 12/23/2022] Open
Abstract
Exercise stimulates immune responses, but the appropriate "doses" for such achievements are unsettled. Conversely, in metabolic tissues, exercise improves the heat shock (HS) response, a universal cytoprotective response to proteostasis challenges that are centred on the expression of the 70-kDa family of intracellular heat shock proteins (iHSP70), which are anti-inflammatory. Concurrently, exercise triggers the export of HSP70 towards the extracellular milieu (eHSP70), where they work as pro-inflammatory cytokines. As the HS response is severely compromised in chronic degenerative diseases of inflammatory nature, we wondered whether acute exercise bouts of different intensities could alter the HS response of lymphocytes from secondary lymphoid organs and whether this would be related to immunoinflammatory responses. Adult male Wistar rats swam for 20 min at low, moderate, high or strenuous intensities as per an overload in tail base. Controls remained at rest under the same conditions. Afterwards, mesenteric lymph node lymphocytes were assessed for the potency of the HS response (42 °C for 2 h), NF-κB binding activity, mitogen-stimulated proliferation and cytokine production. Exercise stimulated cell proliferation in an "inverted-U" fashion peaking at moderate load, which was paralleled by suppression of NF-κB activation and nuclear location, and followed by enhanced HS response in relation to non-exercised animals. Comparative levels of eHSP70 to iHSP70 (H-index) matched IL-2/IL-10 ratios. We conclude that exercise, in a workload-dependent way, stimulates immunoinflammatory performance of lymphocytes of tissues far from the circulation and this is associated with H-index of stress response, which is useful to assess training status and immunosurveillance balance.
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Affiliation(s)
- Thiago Gomes Heck
- Physiology Research Group, Department of Life Sciences, Postgraduate Program in Integral Attention to Health, Regional University of the Northwestern Rio Grande do Sul State, Rua do Comércio, 3000, Ijuí, RS, 98700-000, Brazil.
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil.
| | - Sofia Pizzato Scomazzon
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
- Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133, Rome, Italy
| | - Patrícia Renck Nunes
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
| | - Cinthia Maria Schöler
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
| | - Gustavo Stumpf da Silva
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
| | - Aline Bittencourt
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
| | - Maria Cristina Faccioni-Heuser
- Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Mauricio Krause
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil
| | - Roberto Barbosa Bazotte
- Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil
| | - Rui Curi
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, 05508-900, Brazil
- Institute of Physical Activity Sciences and Sports, Cruzeiro do Sul University, Rua Galvão Bueno, 868 - 13° Andar, Bloco B, Sala 1302, Liberdade, São Paulo, SP, 01506-000, Brazil
| | - Paulo Ivo Homem de Bittencourt
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 2nd floor, suite 350 lab 02, Porto Alegre, RS, 90050-170, Brazil.
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Leite JSM, Cruzat VF, Krause M, Homem de Bittencourt PI. Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions. ACTA ACUST UNITED AC 2016. [DOI: 10.1186/s41110-016-0021-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Adamo M, Codella R, Casiraghi F, Ferrulli A, Macrì C, Bazzigaluppi E, Terruzzi I, Inverardi L, Ricordi C, Luzi L. Active Subjects With Autoimmune Type 1 Diabetes Have Better Metabolic Profiles Than Sedentary Controls. Cell Transplant 2016; 26:23-32. [PMID: 27983910 DOI: 10.3727/096368916x693022] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (-24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.
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Comar JF, de Oliveira DS, Bracht L, Kemmelmeier FS, Peralta RM, Bracht A. The Metabolic Responses to L-Glutamine of Livers from Rats with Diabetes Types 1 and 2. PLoS One 2016; 11:e0160067. [PMID: 27490892 PMCID: PMC4973899 DOI: 10.1371/journal.pone.0160067] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 07/12/2016] [Indexed: 11/18/2022] Open
Abstract
There are several claims about the beneficial effects of supplementing L-glutamine to both type 1 and type 2 diabetes. The purpose of the present study was to provide detailed knowledge about the fate of this amino acid in the liver, the first organ that receives the compound when ingested orally. The study was done using the isolated perfused rat liver, an experimental system that preserves the microcirculation of the organ and that allows to measured several parameters during steady-state and pre steady-state conditions. L-Glutamine was infused in the portal vein (5 mM) and several parameters were monitored. Livers from type 1 diabetic rats showed an accelerated response to L-glutamine infusion. In consequence of this accelerated response livers from type 1 diabetic rats presented higher rates of ammonia, urea, glucose and lactate output during the first 25–30 minutes following L-glutamine infusion. As steady-state conditions approached, however, the difference between type 1 diabetes and control livers tended to disappear. Measurement of the glycogen content over a period of 100 minutes revealed that, excepting the initial phase of the L-glutamine infusion, the increased glucose output in livers from type 1 diabetic rats was mainly due to accelerated glycogenolysis. Livers from type 2 diabetic rats behaved similarly to control livers with no accelerated glucose output but with increased L-alanine production. L-Alanine is important for the pancreatic β-cells and from this point of view the oral intake of L-glutamine can be regarded as beneficial. Furthermore, the lack of increased glucose output in livers from type 2 diabetic rats is consistent with observations that even daily L-glutamine doses of 30 g do not increase the glycemic levels in well controlled type 2 diabetes patients.
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Affiliation(s)
| | | | - Livia Bracht
- Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil
| | | | | | - Adelar Bracht
- Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil
- * E-mail:
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20
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Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis. J Physiol Biochem 2016; 72:643-656. [PMID: 27356529 DOI: 10.1007/s13105-016-0503-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 06/21/2016] [Indexed: 12/21/2022]
Abstract
Exposure to fine particulate matter (PM2.5) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM2.5 over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70-kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM2.5 for additional 12 weeks under the same diet schedule, divided into four groups (n = 14-15 each): Control, PM2.5, HFD, and HFD + PM2.5 were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues. Extracellular to intracellular HSP70 ratio ([eHSP72]/[iHSP70]), viz. H-index, was then calculated. HFD + PM2.5 mice presented a positive correlation between adiposity, increased body weight and glucose intolerance, and increased glucose and triacylglycerol plasma levels. Pancreas exhibited lower iHSP70 expression, accompanied by 3.7-fold increase in the plasma to pancreas [eHSP72]/[iHSP70] ratio. Exposure to PM2.5 markedly potentiated metabolic dysfunction in HFD-treated mice and promoted relevant alteration in cell stress response assessed by [eHSP72]/[iHSP70], a relevant biomarker of chronic low-grade inflammatory state and T2DM risk.
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Pivovarov JA, Taplin CE, Riddell MC. Current perspectives on physical activity and exercise for youth with diabetes. Pediatr Diabetes 2015; 16:242-55. [PMID: 25754326 DOI: 10.1111/pedi.12272] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Revised: 02/05/2015] [Accepted: 02/06/2015] [Indexed: 12/19/2022] Open
Abstract
Regular physical activity (PA) for youth with diabetes improves cardiorespiratory fitness, body composition, bone health, insulin sensitivity, and psychosocial well-being. However many youth with diabetes or pre-diabetes fail to meet minimum PA guidelines and a large percentage of youth with diabetes are overweight or obese. Active youth with type 1 diabetes tend to have lower HbA1c levels and reduced insulin needs, whereas activity in adolescents at-risk for type 2 diabetes improves various measures of metabolism and body composition. Insulin and nutrient adjustments for exercise in type 1 diabetes is complex because of varied responses to exercise type and because of the different times of day that exercise is performed. This review highlights the benefits of exercise and the established barriers to exercise participation in the pediatric diabetes population. A new exercise management algorithm for insulin and carbohydrate intake strategies for active youth with type 1 diabetes is presented.
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Affiliation(s)
- Jacklyn A Pivovarov
- School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, Ontario, Canada
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22
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Codella R, Lanzoni G, Zoso A, Caumo A, Montesano A, Terruzzi IM, Ricordi C, Luzi L, Inverardi L. Moderate Intensity Training Impact on the Inflammatory Status and Glycemic Profiles in NOD Mice. J Diabetes Res 2015; 2015:737586. [PMID: 26347378 PMCID: PMC4541000 DOI: 10.1155/2015/737586] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Accepted: 07/14/2015] [Indexed: 01/13/2023] Open
Abstract
The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic β-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1β were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased α-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window.
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Affiliation(s)
- Roberto Codella
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
- Metabolism Research Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Giacomo Lanzoni
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Alessia Zoso
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Andrea Caumo
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
- Metabolism Research Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Anna Montesano
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Ileana M. Terruzzi
- Division of Metabolic and Cardiovascular Science, Metabolism, Nutrigenomics and Cellular
Differentiation Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Camillo Ricordi
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Livio Luzi
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
- Metabolism Research Center, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | - Luca Inverardi
- Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA
- *Luca Inverardi:
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Cruzat VF, Krause M, Newsholme P. Amino acid supplementation and impact on immune function in the context of exercise. J Int Soc Sports Nutr 2014; 11:61. [PMID: 25530736 PMCID: PMC4272512 DOI: 10.1186/s12970-014-0061-8] [Citation(s) in RCA: 100] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Accepted: 12/04/2014] [Indexed: 01/16/2023] Open
Abstract
Moderate and chronic bouts of exercise may lead to positive metabolic, molecular, and morphological adaptations, improving health. Although exercise training stimulates the production of reactive oxygen species (ROS), their overall intracellular concentration may not reach damaging levels due to enhancement of antioxidant responses. However, inadequate exercise training (i.e., single bout of high-intensity or excessive exercise) may result in oxidative stress, muscle fatigue and muscle injury. Moreover, during the recovery period, impaired immunity has been reported, for example; excessive-inflammation and compensatory immunosuppression. Nutritional supplements, sometimes referred to as immuno-nutrients, may be required to reduce immunosuppression and excessive inflammation. Herein, we discuss the action and the possible targets of key immuno-nutrients such as L-glutamine, L-arginine, branched chain amino acids (BCAA) and whey protein.
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Affiliation(s)
- Vinicius Fernandes Cruzat
- CHIRI Biosciences Research Precinct, Faculty of Health Sciences, School of Biomedical Sciences, Curtin University, GPO Box U1987, Perth, Western Australia Australia
| | - Maurício Krause
- Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS Brazil
| | - Philip Newsholme
- CHIRI Biosciences Research Precinct, Faculty of Health Sciences, School of Biomedical Sciences, Curtin University, GPO Box U1987, Perth, Western Australia Australia
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Elahy M, Baindur-Hudson S, Cruzat VF, Newsholme P, Dass CR. Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy. J Endocrinol 2014; 222:R129-39. [PMID: 24928938 DOI: 10.1530/joe-14-0065] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.
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Affiliation(s)
- Mina Elahy
- College of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, Australia
| | - Swati Baindur-Hudson
- College of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, Australia
| | - Vinicius F Cruzat
- College of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, AustraliaCollege of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, Australia
| | - Philip Newsholme
- College of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, AustraliaCollege of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, Australia
| | - Crispin R Dass
- College of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, AustraliaCollege of Health and BiomedicineVictoria University, St Albans, Victoria 3021, AustraliaSchool of Biomedical SciencesBiosciences Research PrecinctSchool of PharmacyCurtin University, Bentley, Perth, Western Australia 6102, Australia
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25
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Oral supplementations with free and dipeptide forms of l-glutamine in endotoxemic mice: effects on muscle glutamine-glutathione axis and heat shock proteins. J Nutr Biochem 2014; 25:345-52. [DOI: 10.1016/j.jnutbio.2013.11.009] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 11/19/2013] [Accepted: 11/21/2013] [Indexed: 11/21/2022]
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Cruzat VF, Bittencourt A, Scomazzon SP, Leite JSM, de Bittencourt PIH, Tirapegui J. Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia. Nutrition 2013; 30:602-11. [PMID: 24698353 DOI: 10.1016/j.nut.2013.10.019] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2013] [Revised: 09/12/2013] [Accepted: 10/24/2013] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of the present study was to determine the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP) in endotoxemic mice. METHODS B6.129 F2/J mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS], 5 mg/kg, LPS group) and orally supplemented for 48 h with either L-glutamine (1 g/kg) plus L-alanine (0.61 g/kg) (GLN+ALA-LPS group) or 1.49 g/kg DIP (DIP-LPS group). Plasma glutamine, cytokines, and lymphocyte proliferation were measured. Liver and skeletal muscle glutamine, glutathione (GSH), oxidized GSH (GSSG), tissue lipoperoxidation (TBARS), and nuclear factor (NF)-κB-interleukin-1 receptor-associated kinase 1 (IRAK1)-Myeloid differentiation primary response gene 88 pathway also were determined. RESULTS Endotoxemia depleted plasma (by 71%), muscle (by 44%), and liver (by 49%) glutamine concentrations (relative to the control group), which were restored in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Supplemented groups reestablished GSH content, intracellular redox status (GSSG/GSH ratio), and TBARS concentration in muscle and liver (P < 0.05). T- and B-lymphocyte proliferation increased in supplemented groups compared with controls and LPS group (P < 0.05). Tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and IL-10 increased in LPS group but were attenuated by the supplements (P < 0.05). Endotoxemic mice exhibited higher muscle gene expression of components of the NF-κB pathway, with the phosphorylation of IκB kinase-α/β. These returned to basal levels (relative to the control group) in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Higher mRNA of IRAK1 and MyD88 were observed in muscle of LPS group compared with the control and supplemented groups (P < 0.05). CONCLUSION Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice.
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Affiliation(s)
- Vinicius Fernandes Cruzat
- Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Perth, Western Australia.
| | - Aline Bittencourt
- Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, Porto Alegre, Brazil
| | - Sofia Pizzato Scomazzon
- Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, Porto Alegre, Brazil
| | - Jaqueline Santos Moreira Leite
- Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Paulo Ivo Homem de Bittencourt
- Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, Porto Alegre, Brazil
| | - Julio Tirapegui
- Department of Food Science and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
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Impact of exercise and metabolic disorders on heat shock proteins and vascular inflammation. Autoimmune Dis 2012; 2012:836519. [PMID: 23304460 PMCID: PMC3533452 DOI: 10.1155/2012/836519] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2012] [Revised: 09/20/2012] [Accepted: 11/06/2012] [Indexed: 12/27/2022] Open
Abstract
Heat shock proteins (Hsp) play critical roles in the body's self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS), or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia) are associated with type 1 diabetes (an autoimmune disease), type 2 diabetes (the common type of diabetes usually associated with obesity), and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1) reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity.
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Stehno-Bittel L. Organ-based response to exercise in type 1 diabetes. ISRN ENDOCRINOLOGY 2012; 2012:318194. [PMID: 23251813 PMCID: PMC3518066 DOI: 10.5402/2012/318194] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Accepted: 11/14/2012] [Indexed: 12/16/2022]
Abstract
While significant research has clearly identified sedentary behavior as a risk factor for type 2 diabetes and its subsequent complications, the concept that inactivity could be linked to the complications associated with type 1 diabetes (T1D) remains underappreciated. This paper summarizes the known effects of exercise on T1D at the tissue level and focuses on the pancreas, bone, the cardiovascular system, the kidneys, skeletal muscle, and nerves. When possible, the molecular mechanisms underlying the benefits of exercise for T1D are elucidated. The general benefits of increased activity on health and the barriers to increased exercise specific to people with T1D are discussed.
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Affiliation(s)
- Lisa Stehno-Bittel
- Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, KS 66160, USA
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Krause M, Rodrigues-Krause J, O'Hagan C, De Vito G, Boreham C, Susta D, Newsholme P, Murphy C. Differential nitric oxide levels in the blood and skeletal muscle of type 2 diabetic subjects may be consequence of adiposity: a preliminary study. Metabolism 2012; 61:1528-37. [PMID: 22683098 DOI: 10.1016/j.metabol.2012.05.003] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 04/24/2012] [Accepted: 05/02/2012] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Nitric oxide (NO·) exerts key regulatory functions including vasodilation and glucose uptake. Thus reduced NO· levels are associated with insulin resistance and hypertension. In this preliminary work we aimed to measure the levels of NO· metabolites in serum and skeletal muscle of obese and non-obese subjects, with or without type 2 diabetes mellitus (T2DM). METHODS Fifteen sedentary male participants [7 obese controls (C) vs 5 obese and 3 non-obese T2DM; age 54±9 years] were selected according to their BMI (>30 kg/m(2) for obese and 23-27 kg/m(2) for non-obese participants) and evaluated for fasted values of blood glucose, HbA1c, lipid profile, serum CRP (C-reactive protein), erythrocyte glutathione (GSH) metabolism, plasma adiponectin, leptin and cytokines (TNF-α and INFγ), serum and skeletal muscle nitric oxide metabolites (nitrite and nitrates; tNOx) and skeletal muscle nNOS and iNOS expression. Body composition was measured by whole body DEXA and muscle microbiopsy was performed in the vastus lateralis. RESULTS We found that serum tNOx (total nitrite/nitrate; μmol/L) was lower in obese T2DM group (12.7±3.5) when compared with their controls (21.1±2.4), although the non-obese group presented higher concentration of tNOx (33.8±7.2). Skeletal muscle nNOS was higher in obese controls, lower in non-obese T2DM and undetected in obese T2DM. On the other hand, expression of iNOS had an inverse relationship with nNOS, showing higher expression in obese T2DM, decrease in non-obese T2DM and absence in obese control group. tNOx levels (μmol/mg protein) were decreased in the non-obese T2DM group (12.07±0.59) when compared with the obese control (21.68±6.2) and the obese T2DM group (26.3±7.26). CONCLUSION We conclude that the decreased serum NO∙ production in obese T2DM patients seems to be associated with adipose mass as lower adiposity was associated with normal NO∙ which was reduced in the skeletal muscle of the non-obese T2DM patients. We suggest that the lower adiposity (and higher adiponectin) in non-obese T2DM could be responsible for differential levels of NO∙ production and insulin resistance.
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Affiliation(s)
- Mauricio Krause
- Biomedical Research Group, Department of Science, Institute of Technology Tallaght Dublin, Ireland.
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da Silva Krause M, Bittencourt A, Homem de Bittencourt PI, McClenaghan NH, Flatt PR, Murphy C, Newsholme P. Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic β-cell line and mouse islets. J Endocrinol 2012; 214:301-11. [PMID: 22761278 DOI: 10.1530/joe-12-0223] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Interleukin-6 (IL6) has recently been reported to promote insulin secretion in a glucagon-like peptide-1-dependent manner. Herein, the direct effects of IL6 (at various concentrations from 0 to 1000 pg/ml) on pancreatic β-cell metabolism, AMP-activated protein kinase (AMPK) signaling, insulin secretion, nitrite release, and redox status in a rat clonal β-cell line and mouse islets are reported. Chronic insulin secretion (in μg/mg protein per 24 h) was increased from 128·7±7·3 (no IL6) to 178·4±7·7 (at 100 pg/ml IL6) in clonal β-cells and increased significantly in islets incubated in the presence of 5·5 mM glucose for 2 h, from 0·148 to 0·167±0·003 ng/islet. Pretreatment with IL6 also induced a twofold increase in basal and nutrient-stimulated insulin secretion in subsequent 20 min static incubations. IL6 enhanced both glutathione (GSH) and glutathione disulphide (GSSG) by nearly 20% without changing intracellular redox status (GSSG/GSH). IL6 dramatically increased iNOS expression (by ca. 100-fold) with an accompanying tenfold rise in nitrite release in clonal β-cells. Phosphorylated AMPK levels were elevated approximately twofold in clonal β-cells and mouse islet cells. Calmodulin-dependent protein kinase kinase levels (CaMKK), an upstream kinase activator of AMPK, were also increased by 50% after IL6 exposure (in β-cells and islets). Our data have demonstrated that IL6 can stimulate β-cell-dependent insulin secretion via direct cell-based mechanisms. AMPK, CaMKK (an upstream kinase activator of AMPK), and the synthesis of nitric oxide appear to alter cell metabolism to benefit insulin secretion. In summary, IL6 exerts positive effects on β-cell signaling, metabolism, antioxidant status, and insulin secretion.
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31
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Fayh APT, Krause M, Rodrigues-Krause J, Ribeiro JL, Ribeiro JP, Friedman R, Moreira JCF, Reischak-Oliveira A. Effects of L-arginine supplementation on blood flow, oxidative stress status and exercise responses in young adults with uncomplicated type I diabetes. Eur J Nutr 2012; 52:975-83. [PMID: 22763798 DOI: 10.1007/s00394-012-0404-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Accepted: 06/12/2012] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Vascular disease is the principal cause of death and disability in patients with diabetes, and endothelial dysfunction seems to be the major cause in its pathogenesis. Since L-arginine levels are diminished in conditions such as type 1 and type 2 diabetes, in this work we aimed to verify the effects of L-arginine supplementation (7 g/day) over the endothelial function and oxidative stress markers in young male adults with uncomplicated type 1 diabetes. We also investigated the influences of L-arginine administration on vascular/oxidative stress responses to an acute bout of exercise. METHODS Ten young adult male subjects with uncomplicated type 1 diabetes and twenty matched controls volunteered for this study. We analysed the influence of L-arginine supplementation (7 g/day during 1 week) over lower limb blood flow (using a venous occlusion plethysmography technique), oxidative stress marker (TBARS, Carbonyls), anti-oxidant parameters (uric acid and TRAP) and total tNOx in rest conditions and after a single bout of submaximal exercise (VO₂ at 10 % below the second ventilatory threshold). Data described as mean ± standard error (SE). Alpha level was P < 0.05. RESULTS Glycaemic control parameters were altered in type 1 diabetic subjects, such as HbA1c (5.5 ± 0.03 vs. 8.3 ± 0.4 %) and fasted glycaemia (94.8 ± 1.4 vs. 183 ± 19 mg/dL). Oxidative stress/damage markers (carbonyls and TBARS) were increased in the diabetic group, while uric acid was decreased. Rest lower limb blood flow was lower in type 1 diabetic subjects than in healthy controls (3.53 ± 0.35 vs. 2.66 ± 0.3 ml 100 ml⁻¹ min⁻¹). L-Arginine supplementation completely recovered basal blood flow to normal levels in type 1 diabetics' subjects (2.66 ± 0.3 to 4.74 ± 0.86 ml 100 ml⁻¹ min⁻¹) but did not interfere in any parameter of redox state or exercise. CONCLUSION Our findings highlight the importance of L-arginine for the improvement of vascular function in subjects with diabetes, indicating that L-arginine supplementation could be an essential tool for the treatment for the disease complications, at least in non-complicated diabetes. However, based on our data, it is not possible to draw conclusions regarding the mechanisms by which L-arginine therapy is inducing improvements on cardiovascular function, but this important issue requires further investigations.
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Affiliation(s)
- Ana Paula Trussardi Fayh
- Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Newsholme P, Rebelato E, Abdulkader F, Krause M, Carpinelli A, Curi R. Reactive oxygen and nitrogen species generation, antioxidant defenses, and β-cell function: a critical role for amino acids. J Endocrinol 2012; 214:11-20. [PMID: 22547566 DOI: 10.1530/joe-12-0072] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Growing evidence indicates that the regulation of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels is essential for maintaining normal β-cell glucose responsiveness. While long-term exposure to high glucose induces oxidative stress in β cells, conflicting results have been published regarding the impact of ROS on acute glucose exposure and their role in glucose stimulated insulin secretion (GSIS). Although β cells are considered to be particularly vulnerable to oxidative damage, as they express relatively low levels of some peroxide-metabolizing enzymes such as catalase and glutathione (GSH) peroxidase, other less known GSH-based antioxidant systems are expressed in β cells at higher levels. Herein, we discuss the key mechanisms of ROS/RNS production and their physiological function in pancreatic β cells. We also hypothesize that specific interactions between RNS and ROS may be the cause of the vulnerability of pancreatic β cells to oxidative damage. In addition, using a hypothetical metabolic model based on the data available in the literature, we emphasize the importance of amino acid availability for GSH synthesis and for the maintenance of β-cell function and viability during periods of metabolic disturbance before the clinical onset of diabetes.
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Affiliation(s)
- P Newsholme
- School of Biomedical Sciences, Curtin University, PO Box U1987, Perth, Western Australia 6845, Australia.
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Krause MS, McClenaghan NH, Flatt PR, de Bittencourt PIH, Murphy C, Newsholme P. L-arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge. J Endocrinol 2011; 211:87-97. [PMID: 21784771 DOI: 10.1530/joe-11-0236] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In this work, our aim was to determine whether L-arginine (a known insulinotropic amino acid) can promote a shift of β-cell intermediary metabolism favoring glutathione (GSH) and glutathione disulfide (GSSG) antioxidant responses, stimulus-secretion coupling and functional integrity. Clonal BRIN-BD11 β-cells and mouse islets were cultured for 24 h at various L-arginine concentrations (0-1.15 mmol/l) in the absence or presence of a proinflammatory cytokine cocktail (interleukin 1β, tumour necrosis factor α and interferon γ). Cells were assessed for viability, insulin secretion, GSH, GSSG, glutamate, nitric oxide (NO), superoxide, urea, lactate and for the consumption of glucose and glutamine. Protein levels of NO synthase-2, AMP-activated protein kinase (AMPK) and the heat shock protein 72 (HSP72) were also evaluated. We found that L-arginine at 1.15 mmol/l attenuated the loss of β-cell viability observed in the presence of proinflammatory cytokines. L-arginine increased total cellular GSH and glutamate levels but reduced the GSSG/GSH ratio and glutamate release. The amino acid stimulated glucose consumption in the presence of cytokines while also stimulating AMPK phosphorylation and HSP72 expression. Proinflammatory cytokines reduced, by at least 50%, chronic (24 h) insulin secretion, an effect partially attenuated by L-arginine. Acute insulin secretion was robustly stimulated by L-arginine but this effect was abolished in the presence of cytokines. We conclude that L-arginine can stimulate β-cell insulin secretion, antioxidant and protective responses, enabling increased functional integrity of β-cells and islets in the presence of proinflammatory cytokines. Glucose consumption and intermediary metabolism were increased by L-arginine. These results highlight the importance of L-arginine availability for β-cells during inflammatory challenge.
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Affiliation(s)
- Mauricio S Krause
- Biomedical Research Group, Department of Science, Institute of Technology Tallaght, Dublin, Ireland
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Pavlovic S, Zdravkovic N, Dimitrov JD, Djukic A, Arsenijevic N, Vassilev TL, Lukic ML. Intravenous immunoglobulins exposed to heme (heme IVIG) are more efficient than IVIG in attenuating autoimmune diabetes. Clin Immunol 2011; 138:162-71. [DOI: 10.1016/j.clim.2010.10.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Revised: 10/07/2010] [Accepted: 10/29/2010] [Indexed: 01/11/2023]
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Krause M, Rodrigues-Krause JDC. Extracellular heat shock proteins (eHSP70) in exercise: Possible targets outside the immune system and their role for neurodegenerative disorders treatment. Med Hypotheses 2010; 76:286-90. [PMID: 21071151 DOI: 10.1016/j.mehy.2010.10.025] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2010] [Revised: 10/12/2010] [Accepted: 10/13/2010] [Indexed: 11/18/2022]
Abstract
The intracellular heat shock protein 70kDa (iHSP70) is a universal marker of stress protein whose expression is induced by different cell stressors, such as heat, metabolite deprivation, redox imbalances and also during physical exercise. The activation of the iHSP70 is sine qua non for the promotion of tissue repair, since the expression of this chaperone confers cytoprotection and also exerts anti-inflammatory effects. On the other hand, exercise also induces the appearance of HSP70 in the extracellular medium (eHSP70) but, so far, the eHSP70 function has been mainly attributed to the activation of the immune system, seeming to perform an opposite function from the iHSP70. Since a moderate intensity exercise bout induces a general anti-inflammatory response even in the presence of an elevated eHSP70, this protein could carry out other functions rather than immune activation. Because exercise generates heat and metabolic challenges (especially on glucose metabolism) we suggests that the motoneurons, a very active (possibly one of the most stressed cells during exercise) and also very sensitive cells to heat and glucose metabolism imbalances, could be the major sites for the eHSP70 function. Due to the importance of the iHSP70 for repair and stress adaptation, this protein must be present in abundance on the site of stress and, because of its intrinsic inability response to stress [low heat shock factor 1 (HSF-1) activation] and the structure of the motoneurons (very long cells), the iHSP70, produced on the very far nucleus, is not appropriately transported through the axon to the axon terminal, were it is required. Then, during the exercise, the released eHSP70 can be internalized by the motoneurons and act as intracellular chaperons, protecting this cell against oxidative damage, protein denaturation and many others. Since a decreased iHSP70 expression capacity is associated with neurodegeneration diseases (such as Parkinson, polyglutamine, Amyotrophic lateral sclerosis, Alzheimer's, Huntington's and many others), the understanding of the physiological function of the extracellular HSP70 could be helpful on the treatment of neurodegenerative and other neuronal diseases. Besides that, it could explain some of the beneficial effects of the pharmacological HSP70 activators and also the beneficial effects of the exercise among neuronal cells during neurodegenerative-inducing diseases.
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Affiliation(s)
- Mauricio Krause
- Biomedical Research Group, Department of Science, Institute of Technology Tallaght, Dublin, Ireland.
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Expression pattern of thermogenesis-related factors in interscapular brown adipose tissue of alloxan-treated rats: Beneficial effect of l-arginine. Nitric Oxide 2010; 23:42-50. [DOI: 10.1016/j.niox.2010.04.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2010] [Accepted: 04/02/2010] [Indexed: 12/25/2022]
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Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal 2010; 12:537-77. [PMID: 19650713 PMCID: PMC2824521 DOI: 10.1089/ars.2009.2531] [Citation(s) in RCA: 529] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Given their essential function in aerobic metabolism, mitochondria are intuitively of interest in regard to the pathophysiology of diabetes. Qualitative, quantitative, and functional perturbations in mitochondria have been identified and affect the cause and complications of diabetes. Moreover, as a consequence of fuel oxidation, mitochondria generate considerable reactive oxygen species (ROS). Evidence is accumulating that these radicals per se are important in the pathophysiology of diabetes and its complications. In this review, we first present basic concepts underlying mitochondrial physiology. We then address mitochondrial function and ROS as related to diabetes. We consider different forms of diabetes and address both insulin secretion and insulin sensitivity. We also address the role of mitochondrial uncoupling and coenzyme Q. Finally, we address the potential for targeting mitochondria in the therapy of diabetes.
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Affiliation(s)
- William I Sivitz
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Iowa City Veterans Affairs Medical Center and University of Iowa, Iowa City, Iowa, USA.
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Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide. Clin Sci (Lond) 2009; 118:341-9. [PMID: 19922417 DOI: 10.1042/cs20090433] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
It is now widely accepted that hypertension and endothelial dysfunction are associated with an insulin-resistant state and thus with the development of T2DM (Type 2 diabetes mellitus). Insulin signalling is impaired in target cells and tissues, indicating that common molecular signals are involved. The free radical NO* regulates cell metabolism, insulin signalling and secretion, vascular tone, neurotransmission and immune system function. NO* synthesis is essential for vasodilation, the maintenance of blood pressure and glucose uptake and, thus, if levels of NO* are decreased, insulin resistance and hypertension will result. Decreased blood levels of insulin, increased AngII (angiotensin II), hyperhomocysteinaemia, increased ADMA (asymmetric omega-NG,NG-dimethylarginine) and low plasma L-arginine are all conditions likely to decrease NO* production and which are associated with diabetes and cardiovascular disease. We suggest in the present article that the widely reported beneficial effects of exercise in the improvement of metabolic and cardiovascular health are mediated by enhancing the flux of muscle- and kidney-derived amino acids to pancreatic and vascular endothelial cells aiding the intracellular production of NO*, therefore resulting in normalization of insulin secretion, vascular tone and insulin sensitivity. Exercise may also have an impact on AngII and ADMA signalling and the production of pro- and anti-inflammatory cytokines in muscle, so reducing the progression and development of vascular disease and diabetes. NO* synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects.
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