Dependency of acetylcholine-induced insulin release on Ca++ uptake by rat pancreatic islets

The dependency of acetylcholine-induced insulin release on Ca++ uptake from extracellular fluid has been investigated in isolated rat pancreatic islets. Islets were maintained for 46 h in tissue culture, and 45Ca++ uptake and insulin release were measured over 5 min on the same batches of islets. Acetylcholine (10(-10)--10(-6) M) at 2.8 mM glucose stimulated insulin release and Ca++ uptake. Both effects were inhibited by atropine. When acetylcholine-stimulated Ca++ uptake was inhibited by verapamil, a blocker of the voltage-dependent Ca++ channel, acetylcholine-induced insulin release was abolished. In a previous report, verapamil did not inhibit glucose-stimulated insulin release over 5 min despite inhibition of the accompanying Ca++ uptake. Glucose (16.7 mM) stimulated insulin release to a similar extent as acetylcholine. Acetylcholine further enhanced glucose-stimulated insulin release without changing glucose-stimulated Ca++ uptake. Acetylcholine did not significantly alter cAMP levels in the islets. It is concluded that acetylcholine, in contrast to glucose, appears to stimulate the early phase of insulin release by enhancing Ca++ uptake from extracellular fluid. An additional effect of acetylcholine in the presence of high glucose may be operative.