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Richard D. Carr, Marianne O. Larsen, Katarina Jelic, Ola Lindgren, Jenny Vikman, Jens J. Holst, Carolyn F. Deacon, Bo Ahrén, Secretion and Dipeptidyl Peptidase-4-Mediated Metabolism of Incretin Hormones after a Mixed Meal or Glucose Ingestion in Obese Compared to Lean, Nondiabetic Men, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 2, 1 February 2010, Pages 872–878, https://doi.org/10.1210/jc.2009-2054
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Abstract
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/m2) or obese (n = 13; body mass index, 30–35 kg/m2) 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 (AUCtGIP) was not reduced in obese subjects after meal ingestion or oral glucose, AUCiGIP 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 (AUCtGLP-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.
