METABOLIC EFFECTS OF GLIBENCLAMIDE IN ISOLATED RAT HEPATOCYTES IN THEABSENCE OF EXTRACELLULAR CA2+

We examined the metabolic effects of glibenclamide, a potent second-ge neration sulfonylurea, in isolated rat hepatocytes incubated in the ab sence of extracellular Ca2+. We first demonstrated in the present stud y that glibenclamide caused a significant increase in basal glucose re lease and lactate production without any modification of intracellular Ca2+ concentration or cAMP levels in isolated rat hepatocytes. Furthe rmore, glibenclamide inhibited the noradrenaline-induced increase in c AMP accumulation, while activation of glycogenolysis by noradrenaline was not suppressed by this agent. Our data indicate that glibenclamide exerts its metabolic effects independent of intracellular Ca2+ mobili zation and cAMP accumulation.