Protection of rat pancreatic islets by potassium channel openers against alloxan, sodium nitroprusside and interleukin-1β mediated suppression - Possible involvement of the mitochondrial membrane potential

Abstract

Aims/hypothesis. We aimed to study the effects of two KATP channel openers (KCO), diazoxide and the more potent compound NNC 55-0118, on beta-cell suppression and/or toxicity induced by alloxan, sodium nitroprusside and IL-1β. Methods. Islets from rats were exposed to 0.3 mmol/l diazoxide or NNC 55-0118 for 30 min and either alloxan (0.5 mmol/l), sodium nitroprusside (0.5 mmol/l) or IL-1β (12.5 or 25 U/ml) were added and the incubation continued for 30 min. Islets were then washed and incubated for 24 h before examination. Results. After exposure to alloxan, islets showed reduced glucose oxidation rate and impaired glucose-stimulated insulin release. NNC 55-0118 counteracted the effects of alloxan, while diazoxide was less effective. After treatment with sodium nitroprusside, islet glucose oxidation rates were reduced and this was prevented by pretreatment with NNC 55-0118. In short-term experiments the potassium channel openers (KCOs) did not influence the IL-1β effect on insulin secretion. However, long-term addition (24 h) of NNC 55-0118 counteracted IL-1β induced inhibition of the glucose oxidation rate. It was shown, using the fluorescent probe JC-1, that the mitochondrial membrane potential was reduced by the potassium channel openers (KCOs), most strongly by NNC 55-0118. Nevertheless culture with KCOs for 72 h did not cause irreversible damage to the islets. Conclusion/interpretation. Potassium channel openers (KCOs), in particular NNC 55-0118, prevented the toxic effects of alloxan and sodium nitroprusside. IL-1β mediated suppression was reduced by NNC 55-0118 provided the long-term addition of the potassium channel opener (KCO). The protective mechanism of potassium channel openers (KCOs) might involve a decrease of the mitochondrial membrane potential.