The 5'-AMP-activated protein kinase inhibits the transcriptional stimulation by glucose in liver cells, acting through the glucose response complex.
5-Amino-4-imidazolecarboxamide 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 genes, namely L-type pyruvate kinase (L-PK), Spot 14 and fatty acid synthase genes in primary cultured hepatocytes, but was 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.
Leclerc
I
I
Institut Cochin de Génétique Moléculaire, INSERM, Unité 129, Paris, France.
Kahn
A
A
Doiron
B
B
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000378:metabolism*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D011770:Pyruvate Kinase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012265:Ribonucleotides; C051065:THRSP protein, human; C501477:Thrsp protein, mouse; C501478:Thrsp protein, rat; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; D019298:Glucose-6-Phosphate; D064429:Fatty Acid Synthases; D011494:Protein Kinases; C071570:SNF1-related protein kinases; D011770:Pyruvate Kinase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose