title: Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without affecting total adenine nucleotides.
abstract: 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.
authors.affiliation: Hormone and Metabolic Research Unit, Institute of Cellular Pathology, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Beauloye
authors.forename: A S
authors.initials: AS
authors.lastname: Marsin
authors.forename: L
authors.initials: L
authors.lastname: Bertrand
authors.forename: U
authors.initials: U
authors.lastname: Krause
authors.forename: D G
authors.initials: DG
authors.lastname: Hardie
authors.forename: J L
authors.initials: JL
authors.lastname: Vanoverschelde
authors.forename: L
authors.initials: L
authors.lastname: Hue
mesh_terms: D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D009097:Multienzyme Complexes; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases