Sodium nitroprusside inhibits glucose-induced insulin release by activating ATP-sensitive K+ channels

Dual effect of nitric oxide on cytosolic Ca2+concentration and insulin secretion in rat pancreatic β-cells

“…Thus our data suggest that low concentrations of NO potentiate the glucose-induced insulin secretion via the production of cGMP followed by the activation of PKG. This is in good accordance with previous studies showing that cGMP stimulated insulin secretion from rat pancreatic islets (4,15,38).…”

“…Here, it should also be noted that glucose by itself produces NO in pancreatic islets (10,39). Although several researchers showed an inhibitory effect of NO on insulin secretion in the presence of high concentrations of glucose such as 11.1, 16.7, and 20 mM, they did not consider the influence of NO endogenously produced by such high concentrations of glucose on the insulin secretion (4,5,9,35,39). As mentioned above, 11.1 mM glucose is likely to produce a large enough amount of NO to inhibit insulin secretion.…”

“…In contrast, several other groups have reported that NOS inhibitors increase the L-arginine-or glucose-induced insulin secretion from isolated islets of mice (2,18,31,33) and rats (38). Moreover, controversial data showing stimulatory (10,24,27,34,41) and inhibitory (4,9,31,35,38) effects of aqueous NO solution or NO donors, such as 3-morpholinosydnonimine (SIN-1), sodium nitroprusside, and hydroxylamine, on insulin secretion have also been presented.…”

“…We could not rule out that a part of the controversial data hitherto reported concerning the effect of NO on the glucose-induced insulin secretion is due to differences in the concentration of glucose or NO used: In most studies showing an inhibitory effect of NO on the insulin secretion, high concentrations of glucose such as 11.1, 16.7, and 20 mM or millimolar concentrations of NO donors were used for the analyses (4,5,9,12,35). A large amount of NO could be produced by high concentrations of glucose in ␤-cells (34); however, the endogenously produced NO has been ignored in all the studies that investigated the effect of exogenously applied NO on the insulin secretion.…”

Two Distinct Effects of cGMP on Cytosolic Ca2+ Concentration of Rat Pancreatic β-Cells

“…In contrast, several studies revealed that NO donors inhibited the glucose-induced insulin secretion (8 -11). However, some of these studies clearly showed that in contrast to the NO donors, membrane-permeable cGMP analogs facilitated the glucose-induced insulin secretion (9,10). Therefore, the inhibitory effect of NO on the hormone secretion does not appear to be mediated by cGMP.…”