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

Background: Exogenous use of the intestinal hormone glucagon-like
peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin,
inhibition of glucagon, and delay of gastric emptying.Aims: To
assess the effects of endogenous GLP-1 on endocrine pancreatic
secretion and antro-pyloro-duodenal 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 intraduodenal
glucose perfusion at 1 and 2.5 kcal/min, with the higher dose
stimulating GLP-1 release. Antro-pyloro-duodenal 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 glucagon
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 \textgreeka 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
enterogastrone in humans.