Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets.

Abstract

Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP.

Muscarinic receptor modulation of glucose‐induced electrical activity in mouse pancreatic B‐cells

“…Furthermore, the membrane response to acetylcholine was blocked by the muscarinic receptor antagonist atropine. We conclude, in agreement with previous reports [4,6], that acetylcholine exerted its effects on the B-cell membrane exclusively via activation of muscarinic receptors.…”

“…Stimulated Ca 2+ entry has been proposed to be an integral part of this sequence of events [6][7][8]. More recently, however, an important role has also been ascribed to Ca 2+ mobilization from intracellular stores.…”

Distinct effects of acetylcholine and glucose on 45calcium and 86rubidium efflux from mouse pancreatic islets

“…The releasing effect of the neurotransmitter appears to depend entirely on an influx of Ca*+, that can be stimulated only in the presence of a sufficient concentration of glucose, perhaps because the membrane is depolarized by the sugar. These conclusions are in keeping with the evidence that acetylcholine increases the electrical activity triggered by 11 mM glucose in mouse B cells [18,19], but fails to induce it in resting B cells perifused with only 3 mM glucose…”

Protein Kinase C and Calcium Regulation of Adenylyl Cyclase in Isolated Rat Pancreatic Islets

“…However, these latter studies were performed in the absence of a phosphodiesterase inhibitor that is required to detect changes in islet cAMP levels. A lack of effect of acetylcholine on ob/ob mouse islet cAMP levels has also been reported (44); however, ob/ob mouse islets may be deficient in AC isoforms (45).…”