Modulation of acetylcholine-stimulated insulin release by glucose and gastric inhibitory polypeptide.
The interactions of glucose, acetylcholine and gastric inhibitory polypeptide in the regulation of insulin secretion were examined using the in situ perfused rat pancreas. Acetylcholine (1 x 10(-6) M) had no effect on the release of immunoreactive insulin in the presence of 2.2 x 10(-3) M glucose. However, in the presence of 4.4, 6.6 or 8.9 x 10(-3) M glucose, the same concentration of acetylcholine stimulated insulin secretion approximately fourfold. At the highest glucose concentration tested (17.8 x 10(-3) M), the stimulatory effect of acetylcholine on insulin release was less pronounced. The insulin response to acetylcholine was potentiated by the presence of gastric inhibitory polypeptide. This potentiation was most marked when the peptide was present at a concentration of 1 x 10(-9) M, whereas the effect of concomitant infusion of acetylcholine and 2 x 10(-10) M gastric inhibitory polypeptide was only slightly greater than additive. Both atropine (1 x 10(-6) M) and hexamethonium (1 x 10(-4) M) inhibited the insulin response to acetylcholine. However, neither of these cholinergic antagonists had a significant effect on glucose- or gastric inhibitory polypeptide-stimulated insulin secretion. These results demonstrate that the insulinotropic action of acetylcholine is glucose-dependent. A synergistic interaction may exist between acetylcholine and gastric inhibitory polypeptide at the beta-cell which does not involve glucose or gastric inhibitory polypeptide acting on cholinergic receptors in the pancreas. Cholinergic stimulation of insulin secretion in the perfused rat pancreas appears to be mediated by both muscarinic receptors on the beta-cell and nicotinic receptors, presumably on intrapancreatic ganglia.
Verchere
C B
CB
Medical Research Council of Canada, Department of Physiology, University of British Columbia, Vancouver.
Kwok
Y N
YN
Brown
J C
JC
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D006584:Hexamethonium Compounds; D007328:Insulin; D018738:Hexamethonium; D005749:Gastric Inhibitory Polypeptide; D001285:Atropine; D005947:Glucose; D000109:Acetylcholine