Calcium antagonists and islet function. II. Interaction of theophylline and verapamil.

Verapamil inhibits glucose-induced insulin release by the isolated perfused rat pancreas. The dose-response relationship for the inhibitory action of verapamil is shifted to higher concentrations of the drug when the concentration of calcium in the perfusate is increased. The degree of inhibition of glucose-induced insulin release by a given concentration of verapamil decreases as the length of exposure to glucose is increased prior to introduction of the calcium antagonist. Theophylline augments glucose-stimulated insulin release and protects the beta-cell against the inhibitory action of verapamil, both effects of theophylline being dose-related. Even after pretreatment of the pancreas with a high concentration of verapamil, theophylline is able, in the presence of glucose, to stimulate insulin release and, eventually, to restore a nearly normal secretory response to this sugar. We suggest that theophylline, by mobilizing calcium from an organelle-bound pool within the beta-cell, compensates for the verapamil-induced reduction in calcium inward transport into the beta-cell.