Modulation of glucose metabolism by sulfonylureas in primary cultures of adult rat hepatocytes

Addition of tolbutamide (0.1-5 microM) or glipizide (0.05-5 microM) to primary cultures of adult rat hepatocytes caused a dose-dependent increase of fructose 2,6-bisphosphate concentration. This effect was accompanied by a stimulation of the rate of L-lactate production and by an acceleration of the metabolic flux through the reaction catalysed by 6-phosphofructo 1-kinase. Moreover, the continuous presence of tolbutamide during the first 26 hours of culture mimicked long-term insulin effects by raising fructose 2,6-bisphosphate levels and the rate of L-lactate formation. Glucokinase, 6-phosphofructo 1-kinase and total 6-phosphofructo 2-kinase activities were not found to be significantly different in hepatocytes cultured either in the presence or in the absence of sulfonylurea.