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The proglucagon derived glucagon-like peptide-1(7-36)amide (GLP-1) is a gastrointestinal hormone released postprandially from the L cells of the gut. 1 2 It exerts a glucose dependent insulinotropic effect at the pancreatic B cell and lowers glucagon release. 3-5 GLP-1 may also enhance glucose uptake in peripheral tissues 6 and has recently been shown to mediate satiety in humans. 7 8 These combined effects improve glucose tolerance and are the rationale for evaluating its therapeutic potential in the treatment of diabetes mellitus. 9-11
Previous studies in humans have shown that synthetic GLP-1 substantially retards gastric emptying of liquid and solid meals. 11-13 In addition to its insulinotropic and glucagonostatic action, reduction of the gastric emptying rate may be involved in the glucose lowering effect of GLP-1 in healthy subjects and in patients with diabetes mellitus. 11 13 Independent of the tonic pressure generated by the proximal stomach, transpyloric pulsatile flow regulated by the motility of the antro-pyloro-duodenal region is a major mechanism in gastric emptying. 14 15 Antral and especially antro-duodenal coordinated contractions were shown to be associated with the gastric emptying rate of liquids 2 16 17 and solids. 18 Tonic and localised increases in phasic pressure generated by the pylorus provide an important braking mechanism diminishing gastric outflow. 15 19-21
In this study, we have evaluated the effects of graded doses of synthetic GLP-1 on the motility of the antro-pyloro-duodenal region during the interdigestive and postprandial states in humans, the latter being elicited by duodenal perfusion of lipid. Duodenal perfusion of lipid was used instead of oral ingestion of a meal to provide a constant duodenal nutrient load independent of gastric emptying. This particular meal was chosen to establish a stable postprandial motility pattern and to minimise changes in plasma glucose and insulin. The latter are considerable under exogenous GLP-1 and concomitant hyperglycaemia. Finally, we compared the effects of GLP-1 in relation to lipids which is the classic physiological stimulator of pyloric motility.
Material and methods
SUBJECTS
Eleven healthy male volunteers, 23-28 years old and within 10% of ideal body weight, participated in the studies. None was receiving medications and none suffered from gastrointestinal symptoms or any systemic disease. The studies were approved by the ethics committee of the medical faculty of the...