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Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome
Institution:1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States;2. Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, United States;3. Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, OH, United States;4. Metabolic Translational Research Center, Endocrine and Metabolism Institute, Cleveland Clinic, Cleveland, OH, United States;1. Department of Clinical Sciences, Lund University, Lund, Sweden;2. Metabolic Unit, Institute of Neurosciences, National Research Council, Padova, Italy;1. School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston, MA, USA;3. Tehran University of Medical Science, Tehran, Iran;4. Department of Medicine, Section of Endocrinology, Nutrition and Diabetes, Vitamin D, Skin and Bone, Research Laboratory, Boston University Medical Center, Boston, MA, USA;1. Shenzhen Research Institute, Shandong University, Shenzhen 518057, PR China;2. School of Materials Science and Engineering, Shandong University, Jinan 250061, PR China;3. School of Mechanical Engineering, Shandong University, Jinan 250061, PR China;1. Tommy?s Centre for Maternal and Fetal Health, MRC/University of Edinburgh, Centre for Reproductive Health, Queen?s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom;2. School of Nursing, Midwifery and Social Care, Edinburgh Napier University, Sighthill Campus, Edinburgh EH11 4BN, United Kingdom;3. Endocrinology Unit, University/BHF, Centre for Cardiovascular Science, Queen?s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom;1. Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea;2. Department of Neurology, Bundang CHA Medical Center, CHA University School of Medicine, Seongnam, South Korea;3. Department of Neurology, Ewha Womans University, Seoul, South Korea;4. Department of Biostatistics, Yonsei University College of Medicine, Seoul, South Korea
Abstract:Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9 ± 1.2 years, BMI: 34.2 ± 1.1 kg/m2) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60 min/day for 5 days/week at ~85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40 mU/m2/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75 g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P < 0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P < 0.001) and decreased HOMA-IR by 15% (P < 0.05). Training decreased plasma DPP-4 by 10% (421.8 ± 30.1 vs. 378.3 ± 32.5 ng/ml; P < 0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r = ?0.59; P < 0.04), HOMA-IR (r = 0.59; P < 0.04) and fat oxidation (r = ?0.54; P < 0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r = ?0.64; P < 0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome.
Keywords:Impaired glucose tolerance  Obesity  Cytokines  Diabetes
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