Metabolic Effects of Glibenclamide in Isolated Rat Hepatocytes in the Absence of Extracellular Ca²⁺

We examined the metabolic effects of glibenclamide, a potent second-generation sulfonylurea, in isolated rat hepatocytes incubated in the absence of extracellular Ca²⁺. We first demonstrated in the present study that glibenclamide caused a significant increase in basal glucose release and lactate production without any modification of intracellular Ca²⁺ concentration or cAMP levels in isolated rat hepatocytes. Furthermore, glibenclamide inhibited the noradrenaline-induced increase in cAMP 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⁺ mobilization and cAMP accumulation.