GLP-1 regulates gastroduodenal motility involving cholinergic pathways.
The gut-born incretin hormone glucagon-like peptide-1 (GLP-1) delays gastric emptying. To elucidate the mechanisms by which GLP-1 affects gastroduodenal motility and glycaemia, we studied the effects of exendin(9-39), a potent GLP-1 receptor antagonist, on gastroduodenal motility and pancreatic hormones. In this randomized, double-blind, placebo-controlled, four-arm, cross-over trial, 10 healthy volunteers were studied during the interdigestive period followed by duodenal perfusion of a mixed liquid meal (250 kcal). On four separate days, exendin(9-39), atropine, exendin(9-39) + atropine or saline were infused intravenously. Antro-pyloro-duodenal and fundic motility were assessed. The compliance of the proximal stomach was determined by isobaric distensions. During fasting, exendin(9-39) did not influence proximal gastric volume, pyloric tone, and duodenal contractility. Exendin(9-39) significantly increased antral waves only in the absence of atropine. During duodenal meal perfusion, exendin(9-39) significantly reduced proximal gastric volume accommodation, abbreviated postprandial antral inhibition, reduced the postprandial increase in pyloric tone, and reduced gastric compliance. Atropine abolished the effects of exendin(9-39) on gastric volume accommodation but did not affect its effects on postprandial antroduodenal motility and on gastric compliance. Exendin(9-39) increased fasting and postprandial glycaemia and plasma glucagon but not insulin concentrations. Atropine did not affect GLP-1 secretion. Cholinergic mechanisms mediate the effects of GLP-1 on postprandial gastric accommodation but not on antro-pyloro-duodenal motility. GLP-1 reduces fasting and postprandial glycaemia, in part by reducing glucagon secretion.
Schirra
J
J
Department of Internal Medicine II, Ludwig-Maximilians University, Munich, Germany. joerg.schirra@med.uni-muenchen.de
Nicolaus
M
M
Woerle
H J
HJ
Struckmeier
C
C
Katschinski
M
M
Göke
B
B
D000328:Adult; D001285:Atropine / Q000494:pharmacology; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D004435:Eating / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors; D013270:Stomach / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*
D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D006728:Hormones; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D001285:Atropine; D052216:Glucagon-Like Peptide 1