Characterization of acetylcholine-induced insulin secretion in the isolated perfused dog pancreas.

In the presence of a nonstimulatory concentration of glucose, a 60-min perfusion with 50 muM acetylcholine was shown to elicit a monophasic release of insulin in the isolated dog pancreas preparation. A decline in secretory response, which may be due to desensitization of the beta-cell to acetylcholine, was noted during the latter part of the perfusion interval. The potent insulin secretory response elicited by acetylcholine during the 60-min period was abolished 0y 25 muM atropine. Inhibition of the insulinotropic action of acetylcholine was also noted with administration of the mitotic spindle inhibitor, colchicine. When compared to 20-min control perfusions, addition of 1 mM colchicine resulted in a 50% reduction in acetylcholine-induced insulin release. These results suggest that insulin secretion stimulated by acetylcholine can be considered to be due to a muscarinic action of this agent which is dependent, at least in part, upon the microtubular system of the beta-cell.