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

Autor: Lærke S. Gasbjerg, Mette M. Rosenkilde, Amalie R. Lanng, Natasha C. Bergmann, Mikkel B. Christensen, Mads M. Helsted, Jens J. Holst, Maria Buur Nordskov Gabe, Tina Vilsbøll, Simon Veedfald, Bolette Hartmann, Alexander Hovard Sparre-Ulrich, Mette H. Jensen, Filip K. Knop, Signe Stensen
Rok vydání: 2019
Předmět:
Adult
Blood Glucose
Male
0301 basic medicine
endocrine system
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
Incretin
030209 endocrinology & metabolism
Gastric Inhibitory Polypeptide
Carbohydrate metabolism
Glucagon
Receptors
Gastrointestinal Hormone
03 medical and health sciences
0302 clinical medicine
Glucagon-Like Peptide 1
Internal medicine
Insulin Secretion
Internal Medicine
medicine
Humans
Infusions
Intravenous
Glucose tolerance test
medicine.diagnostic_test
Gastric emptying
Chemistry
digestive
oral
and skin physiology
Glucose Tolerance Test
Postprandial Period
Glucagon-like peptide-1
Healthy Volunteers
Peptide Fragments
Glucose
030104 developmental biology
Postprandial
Endocrinology
Gastric Emptying
Blood sugar regulation
hormones
hormone substitutes
and hormone antagonists
Zdroj: Diabetes. 68:906-917
ISSN: 1939-327X
0012-1797
DOI: 10.2337/db18-1123
Popis: 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 ± 16% (A), 30 ± 17% (B), and 8.6 ± 16% (C) compared with D (mean ± 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.
Databáze: OpenAIRE
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