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

Dec 17, 2009The Journal of clinical endocrinology and metabolism

Release and breakdown of gut hormones after a mixed meal or glucose in obese versus lean non-diabetic men

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Abstract

Plasma DPP-4 activity was higher in obese subjects at 38.5 +/- 3.0 mmol/min . microl compared to lean subjects.

Incretin hormone secretion and degradation differ between lean and obese nondiabetic males.
GIP secretion remained unchanged in obese subjects after meal ingestion or oral glucose, but its intact form was lower.
Obese subjects exhibited reduced GLP-1 secretion after both meal ingestion and oral glucose.
The degradation of GIP was increased in obese subjects after meal ingestion, while the degradation of GLP-1 was decreased.
Higher plasma DPP-4 activity in obesity does not correlate with increased overall incretin hormone metabolism.

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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.

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

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