Separate and Combined Gluco-Metabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 in Healthy Individuals

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Lærke S Gasbjerg, Mads M Helsted, Bolette Hartmann, Mette H Jensen, Maria B N Gabe, Alexander H Sparre-Ulrich, Simon Veedfald, Signe Stensen, Amalie R Lanng, Natasha C Bergmann, Mikkel B Christensen, Tina Vilsbøll, Jens J Holst, Mette M Rosenkilde, Filip K Knop

The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted postprandially and contribute importantly to postprandial glucose tolerance. Here, we assessed the individual and combined contributions of endogenous GIP and GLP-1 to the postprandial changes in glucose and gluco-regulatory hormones using the novel GIP receptor antagonist GIP(3-30)NH2 and the well-established GLP-1 receptor antagonist exendin(9-39)NH2During four-hour oral glucose tolerance tests (75 g) combined with an ad libitum meal test, 18 healthy men received on four separate days in randomized, double-blinded order intravenous infusions of A) GIP(3-30)NH2 (800 pmol/kg/min)+exendin(9-39)NH2 (0-20 min: 1,000 pmol/kg/min; 20-240 min: 450 pmol/kg/min), B) GIP(3-30)NH2, C) exendin(9-39)NH2, and D) saline, respectively.Glucose excursions were significantly higher during A than during B, C, and D while glucose excursions during B were higher than during C and D. Insulin secretion (assessed by C-peptide:glucose ratio) was reduced by 37±16% (A), 30±17% (B), and 8.6±16% (C) compared to D (mean±standard deviation). A and C resulted in higher glucagon levels, and faster gastric emptying.In conclusion, endogenous GIP affects postprandial plasma glucose excursions and insulin secretion more than endogenous GLP-1, but the hormones contribute additively to postprandial glucose regulation in healthy individuals.Trial no. ( NCT03133741.

Original languageEnglish
Issue number3
Publication statusPublished - 2019

Bibliographical note

© 2019 by the American Diabetes Association.

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