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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-(737) on gastric emptying in normal volunteers. Nine
healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m2; hemoglobin
A1C 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-(736) amide
(0.4, 0.8, or 1.2 pmol · kg
1 · min1),
GLP-1-(737) (1.2 pmol · kg1 · min1),
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-(736) amide
(P < 0.0001). Effects of
GLP-1-(737) at 1.2 pmol · kg1 · min1
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-(736) amide or -(737)
inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol · kg1 · min1)
still have a significant effect, 3)
despite the known insulinotropic actions of GLP-1-(736) amide and
-(737), 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-(736) amide; pancreatic glucagon; enteroinsular axis
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