Akt2 Regulates Cardiac Metabolism and Cardiomyocyte Survival

The Akt family of serine-threonine kinases participates in diverse cellular processes, including the promotion of cell survival, glucose metabolism, and cellular protein synthesis. All three known Akt family members, Akt1, Akt2 and Akt3, are expressed in the myocardium, although Akt1 and Akt2 are mo...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-10, Vol.281 (43), p.32841-32851
Main Authors: DeBosch, Brian, Sambandam, Nandakumar, Weinheimer, Carla, Courtois, Michael, Muslin, Anthony J.
Format: Article
Language:English
Subjects:
Animals
Apoptosis - genetics
Cell Survival - physiology
Cells, Cultured
Deoxyglucose - metabolism
Deoxyglucose - pharmacokinetics
Hypoglycemic Agents - pharmacology
Insulin - pharmacology
Male
Mice
Mice, Knockout
Myocardial Infarction - etiology
Myocardial Infarction - metabolism
Myocardium - enzymology
Myocardium - metabolism
Myocytes, Cardiac - enzymology
Myocytes, Cardiac - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Time Factors
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Summary:The Akt family of serine-threonine kinases participates in diverse cellular processes, including the promotion of cell survival, glucose metabolism, and cellular protein synthesis. All three known Akt family members, Akt1, Akt2 and Akt3, are expressed in the myocardium, although Akt1 and Akt2 are most abundant. Previous studies demonstrated that Akt1 and Akt3 overexpression results in enhanced myocardial size and function. Yet, little is known about the role of Akt2 in modulating cardiac metabolism, survival, and growth. Here, we utilize murine models with targeted disruption of the akt2 or the akt1 genes to demonstrate that Akt2, but not Akt1, is required for insulin-stimulated 2-[3H]deoxyglucose uptake and metabolism. In contrast, akt2-/- mice displayed normal cardiac growth responses to provocative stimulation, including ligand stimulation of cultured cardiomyocytes, pressure overload by transverse aortic constriction, and myocardial infarction. However, akt2-/- mice were found to be sensitized to cardiomyocyte apoptosis in response to ischemic injury, and apoptosis was significantly increased in the peri-infarct zone of akt2-/- hearts 7 days after occlusion of the left coronary artery. These results implicate Akt2 in the regulation of cardiomyocyte metabolism and survival.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M513087200