Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans

• Published in: American journal of physiology: endocrinology and metabolism Vol. 273; no. 5; pp. E981 - E988
• Main Authors: Nauck, M.A, Niedereichholz, U, Ettler, R, Holst, J.J, Orskov, C, Ritzel, R, Schmiegel, W.H
• Format: Journal Article
• Language: English
• Published: United States 01.11.1997
• Subjects: Adult; Blood Glucose - drug effects; Blood Glucose - metabolism; C-Peptide - blood; C-Peptide - metabolism; DIGESTION; Eating; ESTOMAC; ESTOMAGO; Fasting; Gastric Emptying - drug effects; Gastric Emptying - physiology; Glucagon - administration & dosage; Glucagon - blood; Glucagon - metabolism; Glucagon - pharmacokinetics; Glucagon - pharmacology; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Infusions, Intravenous; Insulin - blood; Insulin - metabolism; Insulin Secretion; Peptide Fragments - administration & dosage; Peptide Fragments - blood; Peptide Fragments - metabolism; Peptide Fragments - pharmacokinetics; Peptide Fragments - pharmacology; Peptides; Postprandial Period; Protein Precursors - administration & dosage; Protein Precursors - blood; Protein Precursors - metabolism; Protein Precursors - pharmacokinetics; Protein Precursors - pharmacology; Reference Values; STOMACH; STOMACH EMPTYING; Time Factors
• ISSN: 0002-9513; 0193-1849; 2163-5773; 1522-1555
• DOI: 10.1152/ajpendo.1997.273.5.e981

1  Department of Medicine, Ruhr-University, Knappschafts-Krankenhaus, 044892 Bochum, Germany; and 2  Departments of Anatomy and Physiology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7 36) amide and GLP-1-(7 37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m 2 ; hemoglobin A 1C 5.0 ± 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7 36) amide (0.4, 0.8, or 1.2 pmol · kg 1 · min 1 ), GLP-1-(7 37) (1.2 pmol · kg 1 · min 1 ), or placebo was infused intravenously from 30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7 36) amide ( P  < 0.0001). Effects of GLP-1-(7 37) at 1.2 pmol · kg 1 · min 1 were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion ( 30 to 0 min) and slightly reduced glucose concentrations. After the meal (0-240 min), integrated incremental glucose ( P  < 0.0001) and insulin responses ( P  = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1 ) GLP-1-(7 36) amide or -(7 37) inhibits gastric emptying also in normal subjects, 2 ) physiological doses (0.4 pmol · kg 1 · min 1 ) still have a significant effect, 3 ) despite the known insulinotropic actions of GLP-1-(7 36) amide and -(7 37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms). incretin hormones; glucagon-like peptide 1-(7 36) amide; pancreatic glucagon; enteroinsular axis