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

Abstract

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 × 10^–6M) had no effect on the release of immunoreactive insulin in the presence of 2.2 × 10^–3M glucose. However, in the presence of 4.4, 6.6 or 8.9 × 10^–3M glucose, the same concentration of acetylcholine stimulated insulin secretion approximately fourfold. At the highest glucose concentration tested (17.8 × 10^–3M), 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 × 10^–9M, whereas the effect of concomitant infusion of acetylcholine and 2 × 10^–10M gastric inhibitory polypeptide was only slightly greater than additive. Both atropine (1 × 10^–6M) and hexamethonium (1 × 10^–4M) 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 β-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 β-cell and nicotinic receptors, presumably on intrapancreatic ganglia.

Modulation of Ca2+ and K+ permeabilities by oxotremorine‐m (Oxo‐m) in rodent pancreatic B‐cells

“…Insulin release induced by cholinergic agents is dependent on external glucose and is accompanied by an increase in [Ca2a-]i (Nenquin, Awouters, Mathot & Henquin, 1984;Verchere, Kwok & Brown, 1991;Rojas, Carroll, Ricordi, Boschero, Stojilkovic & Atwater, 1994). The increase in [Ca21]i is thought to be dependent on the generation of 1P3, which mobilizes Ca2+ from intracellular stores (Malaisse, 1986).…”