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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases
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Adenosine Monophosphate / metabolism
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Adenosine Triphosphate / metabolism
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Animals
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Cell Hypoxia*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Insulin / pharmacology*
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Male
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Multienzyme Complexes / antagonists & inhibitors*
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Multienzyme Complexes / metabolism
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Myocardial Ischemia / metabolism*
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Myocardium / cytology
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Myocardium / enzymology
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Myocardium / metabolism
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / metabolism
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Rats
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Rats, Wistar
Substances
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Enzyme Inhibitors
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Insulin
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Multienzyme Complexes
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Adenosine Monophosphate
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Adenosine Triphosphate
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Protein Serine-Threonine Kinases
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AMP-Activated Protein Kinases