Carbachol modulates GIP-mediated insulin release from rat pancreatic lobules in vitro

Abstract

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.

Modulation of Acetylcholine-Stimulated Insulin Release by Glucose and Gastric Inhibitory Polypeptide

“…McCullough et al [38] had previously suggested that an intact cho linergic innervation was required for the insulinotropic action of GIP since the peptide stimulated insulin release from pancreatic lo bules only in the presence of carbachol. How ever, GIP-stimulated insulin secretion from both the perfused pancreas [11] and isolated islets [24] has been shown to occur in the absence of a cholinergic stimulus.…”

Interactions between cholinergic agonists and enteric factors in the regulation of insulin secretion from isolated perifused rat islets

“…We recently reported that the choliner¬ gic agonist carbachol, in addition to acutely stimu¬ lating insulin secretion in the presence of 5.5 or 7.0 mmol/1 glucose, sensitized the beta-cell to the weak insulin stimulatory effect of 7.5 mmol/1 glu¬ cose (unpublished observations). This sensitization process appears to be mediated by phosphoinositide-derived second messengers and lasts for at least 40 min after carbachof removal.In addition to acetylcholine, the release of vari¬ ous enteric factors, particularly gastric inhibitory polypeptide and cholecystokinin, is thought to participate in the regulation of insulin secretion from the beta-cell (Creutzfeldt 1979;Creutzfeldt & Ebert 1985;McCullough et al 1985;Rushakoff et al 1987). Termed the entero-insular axis (Unger & Eisentraut 1969), this network is thought to play an important role in insulin-mediated fuel homeostasis.…”

“…In addition to acetylcholine, the release of vari¬ ous enteric factors, particularly gastric inhibitory polypeptide and cholecystokinin, is thought to participate in the regulation of insulin secretion from the beta-cell (Creutzfeldt 1979;Creutzfeldt & Ebert 1985;McCullough et al 1985;Rushakoff et al 1987). Termed the entero-insular axis (Unger & Eisentraut 1969), this network is thought to play an important role in insulin-mediated fuel homeostasis.…”