TY - JOUR
T1 - Akt2 regulates cardiac metabolism and cardiomyocyte survival
AU - DeBosch, Brian
AU - Sambandam, Nandakumar
AU - Weinheimer, Carla
AU - Courtois, Michael
AU - Muslin, Anthony J.
PY - 2006/10/27
Y1 - 2006/10/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33845703636&partnerID=8YFLogxK
U2 - 10.1074/jbc.M513087200
DO - 10.1074/jbc.M513087200
M3 - Article
C2 - 16950770
AN - SCOPUS:33845703636
SN - 0021-9258
VL - 281
SP - 32841
EP - 32851
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 43
ER -