Diabetes, Vol 38, Issue 2 198-204, Copyright © 1989 by American Diabetes Association

ARTICLES

Relative importance of extracellular and intracellular Ca2+ for acetylcholine stimulation of insulin release in mouse islets

MP Hermans and JC Henquin
Unit of Diabetology and Nutrition, University of Louvain School of Medicine, Brussels, Belgium.

Mouse islets were used to study whether mobilization of intracellular Ca2+ is sufficient to account for acetylcholine (ACh) amplification of glucose-induced insulin release. In the presence of 15 mM glucose, the acceleration of 45Ca efflux and insulin release by 1-100 microM ACh increased with the concentration of extracellular Ca2+ (0.25-2.5 mM). Low concentrations of the Ca2+-channel blockers D 600 (1 microM) or nifedipine (0.1 microM) partially inhibited glucose-induced insulin release and its amplification by ACh. At higher concentrations, D 600 (25 microM) or nifedipine (2 microM) practically abolished the ionic and secretory effects of 1 microM ACh. However, 100 microM ACh still caused a fast, large, but transient acceleration of 45Ca efflux, accompanied by a small, short-lived release of insulin. Similar results were obtained in a Ca2+-free medium, indicating that this peak of 45Ca efflux reflects Ca2+ mobilization. Addition of nifedipine or omission of Ca2+ during ACh stimulation rapidly and strongly inhibited 45Ca efflux and insulin release. Both glucose and ACh-induced 45Ca uptake were inhibited by D 600. Only high concentrations of ACh (100 microM) mobilize enough cellular Ca2+ to trigger a small and transient insulin release when Ca2+ influx is prevented or impossible. A continuous influx of Ca2+ is necessary for low ACh concentrations to increase release and for high concentrations to have a sustained effect. The amplification of release by the neurotransmitter results from a slight enhancement of Ca2+ influx associated with a marked increase in the effectiveness of incoming Ca2+ on the releasing machinery.
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