Modalities of Gliclazide-induced Ca²⁺ Influx into the Pancreatic B-Cell

The hypoglycemic sulfonylurea gliclazide stimulated ⁴⁵Ca efflux and insulin release from prelabeled and perifused pancreatic rat islets, whether in the absence or presence of glucose (8.3 mM). The gliclazideinduced increase in ⁴⁵Ca efflux is thought to reflect a stimulation of ⁴⁰Ca influx into islet cells; it is suppressed in the absence of extracellular Ca²⁺ or in the presence of the organic Ca²⁺ -antagonist verapamil. In the absence of glucose, the ED₅₀ for the inhibitory action of verapamil on gliclazide-stimulated ⁴⁵Ca efflux was.almost identical to that found when the process of ⁴⁰Ca-⁴⁵Ca exchange was stimulated by an increase in the extracellular concentration of K⁺, a procedure that leads to the depolarization of the plasma membrane. .In the presence of glucose, however, the cationic response to gliclazide displayed an increased sensitivity toward the inhibitory action of verapamil. It is proposed that hypoglycemic sulfonylureas facilitate Ca²⁺ inflow into islet cells mainly through voltage-sensitive Ca²⁺ channels. In the presence of glucose, however, the stimulant action of hypoglycemic sulfonylureas upon Ca²⁺ entry into islet cells may entail a modality of Ca²⁺ transport not identical to that evoked by depolarization of the plasma membrane.