Calcium antagonists and islet function. I. Inhibition of insulin release by verapamil.

Verapamil is a potent calcium antagonist known to inhibit excitation-contraction coupling in both myocardium and myometrium. Its effect upon glucose- and sulfonylurea-induced insulin release was investigated in the isolated perfused rat pancreas. After twenty-five minutes' pretreatment and at concentrations ranging between 0.8 and 8.1 muM, verapamil caused a dose-related inhibition of glucose-induced insulin release during both the early and late phase of the secretory process. At a concentration of 0.8 muM, the degree of inhibition was more marked when the exposure time to verapamil prior to stimulation with glucose was increased to sixty minutes. Verapamil also inhibited gliclazide-induced insulin release. Infusion of verapamil during the late phase of the secretory response to glucose demonstrated that the inhibition of insulin release was an immediate and reversible phenomenon. The inhibitory effect of verapamil was enhanced at a subnormal calcium concentration and reduced at a high calcium concentration. These findings are consistent with the well-known calcium dependency of both glucose- and sulfonylurea-induced insulin release and suggest that verapamil might be a promising tool for further studies on the interactions between cations and secretagogues in the beta-cell secretory process.