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GLP‐1 regulates gastroduodenal motility involving cholinergic pathways
Author(s) -
Schirra J.,
Nicolaus M.,
Woerle H. J.,
Struckmeier C.,
Katschinski M.,
Göke B.
Publication year - 2009
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2008.01246.x
Subject(s) - postprandial , medicine , atropine , endocrinology , gastric emptying , stomach , cholecystokinin , insulin , receptor
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.