Publication:

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.