The 5′-AMP-activated protein kinase inhibits the transcriptional stimulation by glucose in liver cells, acting through the glucose response complex

5-Amino-4-imidazolecarbosamide riboside (AICAR) is known to stimulate rat liver 5'-AMP-activated protein kinase (AMPK). AMPK is the mammalian homologue of Snf1p in yeast, involved in derepression of glucose-repressed genes.We used AICAR to test if AMPK could also play a role in the regulation of glucose-dependent genes in mammalian cells. At a concentration which induces phosphorylation-dependent inactivation of HMG-CoA reductase, AICAR blocked glucose activation of three glucose responsive gents, namely L-type pyruvate kinase (L-PK), Spot 14 and fatty acid synthase genes in primary cultured hepatocytes, but nas without any action on glucose phosphorylation to glucose 6-phosphate and on expression of PEPCK, albumin and beta-actin genes. AICAR was also found to inhibit activation of the L-PK gene promoter by glucose in transiently transfected hepatoma cells, Therefore our results suggest that AMPK is probably involved in the glucose signal pathway regulating gene expression in the liver. (C) 1998 Federation of European Biochemical Societies.