Insulin antagonizes AMP‐activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides

FEBS Letters

Hardie, D.Grahame²  Hue, Louis¹  Bertrand, Luc¹  Marsin, Anne-Sophie¹  Vanoverschelde, Jean-Louis³  Krause, Ulrike¹  Beauloye, Christophe¹ 

[1]Hormone and Metabolic Research Unit, Institute of Cellular Pathology, 75 Avenue Hippocrate, ICP-UCL 7529, B-1200 Brussels, Belgium

[2]Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK

[3]Division of Cardiology, University of Louvain Medical School, Brussels, Belgium

关键词: AMP-activated protein kinase;    Heart;    Ischemia;    Anoxia;    Insulin;    AMPK;    AMP-activated protein kinase;    AMPKK;    AMP-activated protein kinase kinase;    PCr;    phosphocreatine;    Cr;    creatine;    ACC;    acetyl-CoA carboxylase;    PI3K;    phosphatidylinositol-3-kinase;   

DOI  :  10.1016/S0014-5793(01)02788-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

AMP-activated protein kinase (AMPK) is known to be activated by phosphorylation on Thr172 in response to an increased AMP/ATP ratio. We report here that such an activation indeed occurred in anaerobic rat hearts and that it was antagonized (40–50%) when the hearts were pre-treated with 100 nM insulin. The effect of insulin (1) was blocked by wortmannin, an inhibitor of phosphatidylinositol-3-kinase; (2) only occurred when insulin was added before anoxia, suggesting a hierarchical control; (3) resulted in a decreased phosphorylation state of Thr172 in AMPK and (4) was unrelated to changes in the AMP/ATP ratio. This is the first demonstration that AMPK activity could be changed without a detectable change in the AMP/ATP ratio of the cardiac cell.

【 授权许可】

Unknown