Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men

J Clin Endocrinol Metab. 2010 Feb;95(2):872-8. doi: 10.1210/jc.2009-2054. Epub 2009 Dec 11.


Context: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activity of DPP-4 may be increased in obesity. The impact of this increase on incretin hormone secretion and metabolism is not known.

Objective: The aim of the study was to assess incretin hormone secretion and degradation in lean and obese nondiabetic subjects.

Design, settings, and participants: We studied the ingestion of a mixed meal (560 kcal) or oral glucose (2 g/kg) in healthy lean (n = 12; body mass index, 20-25 kg/m(2)) or obese (n = 13; body mass index, 30-35 kg/m(2)) males at a University Clinical Research Unit.

Main outcome measures: We measured the area under the curve of plasma intact (i) and total (t) GIP and GLP-1 after meal ingestion and oral glucose.

Results: Plasma DPP-4 activity was higher in the obese subjects (38.5 +/- 3.0 vs. 26.7 +/- 1.6 mmol/min . microl; P = 0.002). Although GIP secretion (AUC(tGIP)) was not reduced in obese subjects after meal ingestion or oral glucose, AUC(iGIP) was lower in obese subjects (8.5 +/- 0.6 vs. 12.7 +/- 0.9 nmol/liter x 300 min; P < 0.001) after meal ingestion. GLP-1 secretion (AUC(tGLP-1)) was reduced in obese subjects after both meal ingestion (7.3 +/- 0.9 vs. 10.0 +/- 0.6 nmol/liter x 300 min; P = 0.022) and oral glucose (6.6 +/- 0.8 vs. 9.6 +/- 1.1 nmol/liter x 180 min; P = 0.035). iGLP-1 was reduced in parallel to tGLP-1.

Conclusions: 1) Release and degradation of the two incretin hormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestion and oral glucose, whereas GIP but not GLP-1 metabolism is increased after meal ingestion. 2) Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin hormone metabolism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / pharmacology
  • Adult
  • Area Under Curve
  • Dipeptidyl Peptidase 4 / physiology*
  • Food
  • Gastric Inhibitory Polypeptide / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / administration & dosage*
  • Humans
  • Insulin Resistance
  • Male
  • Obesity / metabolism*
  • Thinness / metabolism*
  • Young Adult


  • Acetaminophen
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Glucose