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.


OBJECTIVE
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 alpha 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.
Department of Internal Medicine II, Clinical Research Unit, Ludwig-Maximilians University, Marchioninistr 15, Munich 81377, Germany. Joerg.Schirra@med.uni-muenchen.de
J
J
Schirra
M
M
Nicolaus
R
R
Roggel
M
M
Katschinski
M
M
Storr
H J
HJ
Woerle
B
B
Göke
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004386:Duodenum / Q000502:physiology; D005215:Fasting / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008365:Manometry / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D019518:Postprandial Period / Q000502:physiology; D011706:Pyloric Antrum / Q000502:physiology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors
D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1