The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester potentiates insulin secretion stimulated by glucose and L-arginine independently of its action on ATP-sensitive K+ channels.

The nature of the action of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on hormone release from isolated islets was investigated. We found that glucose-induced insulin release was potentiated by L-NAME in the absence or presence of diazoxide, a potent K+ATP channel opener, as well as in the presence of diazoxide plus a depolarizing concentration of K+. At a low, physiological glucose concentration L-NAME did not influence insulin secretion induced by K+ but inhibited glucagon secretion. L-arginine-induced insulin release was potentiated by L-NAME. This potentiation was observed also in the presence of K+ plus diazoxide. Further, glucagon release induced by L-arginine as well as by L-arginine plus K+ and diazoxide was suppressed by L-NAME. The results strongly suggest that the L-NAME-induced potentiation of insulin secretion in response to glucose or L-arginine as well as the inhibitory effects on glucagon secretion are largely mediated by L-NAME directly suppressing islet NOS activity. Hence NO apparently affects insulin and glucagon secretion independently of membrane depolarization events.