M. H. Antoine

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 86Rb outflow from perifused islets. This effect persisted in the absence of external Ca2+ but was impaired by glibenclamide. Hydroxylamine decreased 45Ca 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 45Ca 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.

Synthesis and biological evaluation of sulfonylcyanoguanidines and sulfonamidonitroethylenes as bioisosteres of hypoglycemic sulfonylureas

Summary Sulfonylcyanoguanidines and sulfonamidonitroethylenes are bioisosteres of hypoglycemic sulfonylureas and were prepared and evaluated for their insulin release potency from rat pancreatic islets. At 25 μM, both bioisosteres of glibenclamide, sulfonylcyanoguanidine 22 and sulfonamidonitroethylene 23 , were as potent as their parent on insulin secretion.