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.
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
M
M
Emoto
Y
Y
Inoue
K
K
Kaku
T
T
Kaneko
D000818:Animals; D006528:Carcinoma, Hepatocellular; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005943:Gluconeogenesis; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013873:Thionucleotides; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D014044:Tolbutamide; D000242:Cyclic AMP; D010729:Phosphoenolpyruvate Carboxykinase (GTP)