Tolbutamide and insulin stimulation of fructose-2,6-bisphosphate formation in hepatocytes differ

The effects of tolbutamide and pancreatic hormones on liver fructose-2,6-bisphosphate (F-2,6-P2) formation were examined using isolated rat hepatocytes. Glucagon decreased the F-2,6-P2 level in a dose-dependent manner. Insulin (greater than 10(-9) M) increased the F-2,6-P2 level reduced by glucagon (less than 10(-9) M), but did not show a stimulatory effect on this activator formation in the absence of glucagon. On the other hand, tolbutamide increased the F-2,6-P2 level in hepatocytes regardless of the presence or absence of glucagon. Tolbutamide (2 mM) stimulation on liver F-2,6-P2 formation was enhanced by the concomitant addition of insulin (10(-8) M) in the presence of glucagon (3 X 10(-11) M). These observations suggest that the regulatory effect of tolbutamide on liver F-2,6-P2 level is independent of that of insulin.