Hydroxylamine, a nitric oxide donor, inhibits insulin release and activates K-ATP(+) channels

The present study was undertaken to assess the effects of hydroxylamine, a nitric oxide (NO) donor, on ionic and secretory events in rat pancreatic islets. Hydroxylamine provoked a concentration-dependent inhibition of the glucose-induced insulin release. This inhibitory action was counteracted by glibenclamide. Moreover, hydroxylamine increased the rate of Rb-86 outflow from perifused islets. This effect persisted in the absence of external Ca2+ but was impaired by glibenclamide. Hydroxylamine decreased Ca-45 outflow, [Ca2+](i) and insulin output from islets exposed to 16.7 mM glucose and extracellular Ca2+. By contrast hydroxylamine did not affect the increase in Ca-45 outflow and [Ca2+](i) evoked by K+ depolarization. These experimental results suggest that the negative insulinotropic action of the NO donor results, at least in part, from the activation of ATP-sensitive K+ channels leading to a decrease in Ca2+ influx and [Ca2+](i). Additional mechanisms, however, could also be involved in the NO donor modulation of the secretory process.