Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients.
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.
Boschmann
Michael
M
Franz-Volhard Clinical Research Center, Helios Klinikum and Medical Faculty of the Charité, D-13125 Berlin, Germany.
Engeli
Stefan
S
Dobberstein
Kerstin
K
Budziarek
Petra
P
Strauss
Anke
A
Boehnke
Jana
J
Sweep
Fred C G J
FC
Luft
Friedrich C
FC
He
Yanling
Y
Foley
James E
JE
Jordan
Jens
J
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
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane; D009638:Norepinephrine