Study of influence of nicorandil on hypoglycemic action of glibenclamide in alloxan induced diabetic rats

Background: To assess the interaction between ATP - sensitive potassium channel opener nicorandil and potassium channel blocker glibenclamide in alloxan - induced diabetic rats and to evaluate whether nicorandil antagonizes the oral hypoglycaemic action of glibenclamide.Methods: Insulin secretion involves ATP sensitive K+ channel blockade, the influence of ATP sensitive K+ channel opener was studied in combination with its blocker. Albino rats of wistar strain, weighing between 200 - 250 grams of either sex were used for the study. Diabetes was induced by injecting alloxan monohydrate 2% solution intra - peritoneally in a dose of 150 mg/kg body weight. Animals with fasting blood glucose between 200 - 300 mg/dl were selected and were divided into 3 groups of six animals each. Group I received 2% gum acacia, group II was given glibenclamide (0.5 mg/kg body weight) and group III was treated with nicorandil (0.3 mg/kg body weight) + glibenclamide (0.5 mg/kg body weight) respectively orally for 30 days. Fasting blood sugar was recorded in all rats on 1st, 3rd, 7th, 14th, 21st and 28th days.Results: Results show that glibenclamide has significantly reduced the blood sugar levels (P<0.05), whereas when glibenclamide was combined with nicorandil there was a significant rise in blood sugar level (P<0.05).Conclusions: The study shows that hypoglycaemic action of glibenclamide is antagonized by nicorandil as indicated by worsening of diabetes, probably by blocking the K+ channel closing action of glibenclamide. These findings suggest that K+ channel openers should be avoided with K+ channel blockers in presence of diabetes.