Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men.

Context: Glucose-dependent insulinotropic polypeptide(GIP) and glucagon-like peptide-1(GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activityof DPP-4 may be increased in obesity. The impact of this increase on incretinhormone secretion and metabolism is not known. Objective: The aim of the study was to assess incretinhormone secretion and degradation in lean and obese nondiabetic subjects. Design, Settings, and Participants: We studied the ingestionof 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 ingestionand oral glucose. Results: Plasma DPP-4 activity was higher in the obese subjects (38.5 +/- 3.0 vs. 26.7 +/- 1.6 mmol/min . mul; P = 0.002). Although GIP secretion (AUCtGIP) was not reduced in obese subjects after meal ingestionor oral glucose, AUCiGIP 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 (AUCtGLP-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 incretinhormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestionand 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 incretinhormone metabolism.