Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals

TY - JOUR

T1 - Separate and Combined Glucometabolic Effects of Endogenous Glucose-Dependent Insulinotropic Polypeptide and Glucagon-like Peptide 1 in Healthy Individuals

AU - Gasbjerg, Lærke S

AU - Helsted, Mads M

AU - Hartmann, Bolette

AU - Jensen, Mette H

AU - Gabe, Maria B N

AU - Sparre-Ulrich, Alexander H

AU - Veedfald, Simon

AU - Stensen, Signe

AU - Lanng, Amalie R

AU - Bergmann, Natasha C

AU - Christensen, Mikkel B

AU - Vilsbøll, Tina

AU - Holst, Jens J

AU - Rosenkilde, Mette M

AU - Knop, Filip K

N1 - © 2019 by the American Diabetes Association.

PY - 2019

Y1 - 2019

N2 - 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. In this study, we assessed the individual and combined contributions of endogenous GIP and GLP-1 to the postprandial changes in glucose and glucoregulatory hormones using the novel GIP receptor antagonist GIP(3-30)NH2 and the well-established GLP-1 receptor antagonist exendin(9-39)NH2. During 4-h 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) plus 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 6 16% (A), 30 6 17% (B), and 8.6 6 16% (C) compared with D (mean 6 SD). 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.

AB - 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. In this study, we assessed the individual and combined contributions of endogenous GIP and GLP-1 to the postprandial changes in glucose and glucoregulatory hormones using the novel GIP receptor antagonist GIP(3-30)NH2 and the well-established GLP-1 receptor antagonist exendin(9-39)NH2. During 4-h 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) plus 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 6 16% (A), 30 6 17% (B), and 8.6 6 16% (C) compared with D (mean 6 SD). 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.

U2 - 10.2337/db18-1123

DO - 10.2337/db18-1123

M3 - Journal article

C2 - 30626611

SN - 0012-1797

VL - 68

SP - 906

EP - 917

JO - Diabetes

JF - Diabetes

IS - 3

ER -