TITLE

Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro- duodenal motility in humans

AUTHOR(S)
Schirra, J.; Nicolaus, M.; Roggel, R.; Katschinski, M.; Storr, M.; Woerle, H. J.; Göke, B.
PUB. DATE
February 2006
SOURCE
Gut;Feb2006, Vol. 55 Issue 2, p243
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1 ) lowers glycaemia by stimulation of insulin, inhibition of glucogon, and deice, of gastric emptying. Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloroduodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2). Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9–39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenel glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloroduodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments. Results: Ex(9–39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9–39)NH2 raised plasma glucogon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9–39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation. Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic α cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogostrone in humans.
ACCESSION #
19552435

 

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