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.
Emoto
M
M
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Inoue
Y
Y
Kaku
K
K
Kaneko
T
T
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)