@article{cbae1030334011df8ed1000ea68e967b,
title = "Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men",
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 (AUC tGIP) 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 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 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.",
author = "Carr, {Richard D} and Larsen, {Marianne O} and Katarina Jelic and Ola Lindgren and Jenny Vikman and Holst, {Jens J} and Deacon, {Carolyn F} and Bo Ahr{\'e}n",
note = "Keywords: Acetaminophen; Adult; Antigens, CD26; Area Under Curve; Food; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Humans; Insulin Resistance; Male; Obesity; Thinness; Young Adult",
year = "2010",
month = feb,
doi = "10.1210/jc.2009-2054",
language = "English",
volume = "95",
pages = "872--8",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "2",
}
