title: Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome.
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±1.1kg/m(2)) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/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 (40mU/m(2)/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g 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±32.5ng/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.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.forename: Hazel
authors.initials: H
authors.lastname: Huang
authors.forename: Anny
authors.initials: A
authors.lastname: Mulya
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Kashyap
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001823:Body Composition; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005081:Exercise Therapy; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000628:therapy*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000628:therapy*; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4
keywords: Akt; Cytokines; Diabetes; Impaired glucose tolerance; Obesity; PPAR-α; SREBP-1c; TNF-α; peroxisome proliferator-activated receptor alpha; protein kinase B; sterol retinol-element binding protein one c; tumor necrosis factor alpha