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

FEBS Letters

Doiron, Bruno¹  Leclerc, Isabelle¹  Kahn, Axel¹ 

[1] Institut Cochin de Génétique Moléculaire, INSERM, Unité 129, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France

关键词: 5′-AMP-activated protein kinase;    5-Amino-4-imidazolecarboxamide riboside;    Glucose;    Pyruvate kinase gene;   

DOI  :  10.1016/S0014-5793(98)00745-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 β-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.

【 授权许可】

Unknown