The inhibitory effect of tolbutamide on phosphoenolpyruvate carboxykinase activity in rat hepatoma H4IIE cells.

Effects of tolbutamide on the activity of hepatic phosphoenolpyruvate carboxykinase (PEPCK), a rate limiting enzyme in gluconeogenesis, was examined using rat hepatoma (H4IIE) cells. Tolbutamide inhibited PEPCK activity induced by cAMP in a time- and dose-dependent manner. Tolbutamide effect was rapidly exerted and insulin-independent. The inhibitory effect of 5 mM tolbutamide corresponded with that of 10(-7) M insulin. These results suggest the possibility that tolbutamide plays a significant role on amelioration of the deranged glucose metabolism in the liver through repression of gluconeogenesis, primarily due to the inhibition of PEPCK activity.