The glucagon-like peptide 1 inhibition of gastric emptying
outweighs its insulinotropic effects in healthy humans.
Nauck, Michael A., Ulrich Niedereichholz, Rainer Ettler, Jens Juul
Holst, Cathrine Orskov, Robert Ritzel, and Wolff H. Schmiegel.
Department of Medicine, Ruhr-University, Knappschafts-Krankenhaus,
Bochum, Germany; Departments of Anatomy and Physiology, Panum
Institute, University of Copenhagen, Denmark
APStracts 4:0165E, 1997.
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 [7-37] on
gastric emptying in normal volunteers. Nine healthy subjects
participated (26 SONDZEICHEN 177 \f "MT Symbol" 3 y.; BMI
22.9 SONDZEICHEN 177 \f "MT Symbol" 1.6 kg/m2; HbA1c 5.0
SONDZEICHEN 177 \f "MT Symbol" 0.2 %) in 5 experiments on
separate occasions after an overnight fast. A nasogastric tube was
positioned for the determination of gastric volume using a dye
-dilution technique (phenol red). GLP-1 [7-36 amide] (0.4, 0.8, or 1.2
pmol/kg/min), GLP-1 [7-37] (1.2 pmol/kg/min) or placebo were 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/min) were virtually identical.
GLP-1 dose-dependently stimulated fasting insulin secretion (-30 to 0
min) and slightly reduced glucose concentrations. After the meal (0
to 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]
inhibit gastric emptying also in normal subjects, (2) physiological
doses (0.4 pmol/kg/min) 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).
Received 25 February 1997; accepted in final form 24 July 1997.
APS Manuscript Number E90-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997