Carbachol modulates GIP-mediated insulin release from rat pancreatic lobules in vitro.
Rat pancreatic lobules were used to investigate the interaction of gastric inhibitory polypeptide (GIP), carbachol, glucose, and an amino acid mixture on insulin secretion. At 5 mM glucose, GIP (1.1 ng/ml) did not augment insulin secretion in the presence or absence of carbachol (5 X 10(-5)M) during a 210-min incubation. However, at 11 mM glucose, GIP did augment insulin secretion in the presence (342.5 +/- 62.0 vs. 212.5 +/- 50.5 microU . ml-1 . mg tissue-1, mean +/- SE; P less than 0.01) but not the absence (217.0 +/- 45.5 vs. 205.8 +/- 35.0 microU . ml-1 . mg tissue-1) of carbachol. During subsequent 30-min incubations, GIP was increased to a supra-physiological concentration of 11 ng/ml and again augmented insulin secretion with (65.8 +/- 10.8 vs. 27.8 +/- 2.4 microU . ml-1 . mg tissue-1 . h-1; P less than 0.001) but not without (37.2 +/- 1.8 vs. 30.2 +/- 2 microU . ml-1 . mg-1 tissue-1 . h-1) carbachol present. This GIP-mediated insulin secretion was blocked by atropine (34.8 to 1.8 vs. 37.6 +/- 1.6 microU . ml-1 . mg tissue-1 . h-1). At amino acid concentrations of 21 and 211 mM, but not 2.1 mM, GIP augmented insulin release but again only with carbachol present. In conclusion, porcine GIP augments amino acid as well as glucose-mediated insulin secretion in vitro. Furthermore, this biological action is dependent on an, as yet, unidentified cholinergic mechanism. The pathophysiological significance of the neural-hormonal interaction deserves further investigation.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D005749:Gastric Inhibitory Polypeptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013997:Time Factors
D000596:Amino Acids; D005768:Gastrointestinal Hormones; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D001285:Atropine; D002217:Carbachol; D005947:Glucose