title: Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients.
abstract: BACKGROUND
  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 extrapancreatic mechanisms.
  
  
  OBJECTIVE
  We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism.
  
  
  METHODS
  We conducted a randomized, double-blind, crossover study at an academic clinical research center.
  
  
  METHODS
  Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m(2), participated.
  
  
  METHODS
  INTERVENTION included 7 d treatment with the selective DPP-4 inhibitor vildagliptin or placebo and a standardized test meal on d 7.
  
  
  METHODS
  Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin, dialysate glucose, lactate, pyruvate, glycerol were measured.
  
  
  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, vildagliptin 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.
authors.affiliation: Franz-Volhard Clinical Research Center, Helios Klinikum and Medical Faculty of the Charité, D-13125 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Boschmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Engeli
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dobberstein
authors.forename: Petra
authors.initials: P
authors.lastname: Budziarek
authors.forename: Anke
authors.initials: A
authors.lastname: Strauss
authors.forename: Jana
authors.initials: J
authors.lastname: Boehnke
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Yanling
authors.initials: Y
authors.lastname: He
authors.forename: James E
authors.initials: JE
authors.lastname: Foley
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008053:Lipid Mobilization / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D010084:Oxidation-Reduction; D019518:Postprandial Period / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology*; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane; D009638:Norepinephrine