Glyburide priming of beta cells. Possible involvement of phosphoinositide hydrolysis

In the simultaneous presence of 5.5 mM glucose, exposure of isolated perifused islets to the sulfonylurea glyburide (500 nM) acutely stimulated insulin release and amplified the subsequent insulin secretory responses to 10 mM glucose or 10 mM arginine. This sensitizing effect of glyburide developed within 10 min, was maintained for at least 40 min after glyburide removal from the perifusion medium, and was attenuated by the calcium channel blocker nitrendipine. In islets whose inositol-containing lipids were prelabeled during a 2-hr incubation period with myo[2-3H]inositol, glyburide induced a concentration-dependent increase in labeled inositol phosphate accumulation. Nitrendipine abolished this stimulatory effect of glyburide. In perifused islets, the stimulatory effect of glyburide on phosphoinositide (PI) hydrolysis persisted after its removal from the medium and the duration of this effect paralleled the duration of sensitization. These findings suggest that glyburide-induced increases in PI hydrolysis account, at least in part, for its acute stimulatory effect on insulin output and its ability to sensitize islets to subsequent stimulation.