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Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients

Item Type:Article
Title:Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients
Creators Name:Boschmann, M. and Engeli, S. and Dobberstein, K. and Budziarek, P. and Strauss, A. and Boehnke, J. and Sweep, F.C. and Luft, F.C. and He, Y. and Foley, J.E. and Jordan, J.
Abstract:Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study Setting: Academic clinical research center Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2) Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main outcome measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.
Keywords:Microdialysis, Adipose Tissue, Skeletal Muscle, Sympathetic, Cross-Over Studies, Type 2 Diabetes Mellitus, Dipeptidyl-Peptidase IV Inhibitors, Double-Blind Method, Glucagon-Like Peptide 1, Hypoglycemic Agents, Lipid Mobilization, Nitriles, Norepinephrine, Oxidation-Reduction, Postprandial Period, Pyrrolidines
Source:Journal of Clinical Endocrinology and Metabolism
ISSN:0021-972X
Publisher:Endocrine Society (U.S.A.)
Volume:94
Number:3
Page Range:846-852
Date:March 2009
Official Publication:https://doi.org/10.1210/jc.2008-1400
PubMed:View item in PubMed

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