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

摘要

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 · μl; 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 × 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 × 300 min; P = 0.022) and oral glucose (6.6 ± 0.8 vs . 9.6 ± 1.1 nmol/liter × 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.