Role of Akt in cardiac growth and metabolism.
The Akt family of intracellular protein kinases regulates cellular growth, proliferation, survival and metabolism. Postnatal growth of the heart chiefly involves non-proliferative cardiac myocyte enlargement analogous to skeletal muscle growth. Cardiac hypertrophy exists in a 'physiological' form that is an adaptive response to long-term exercise training, and as a 'pathological' form that is often a maladaptive response to hypertension or valvular heart disease. By use of an Akt1-deficient mouse model system, we determined that Akt1 activity is required for physiologic cardiac growth in response to insulin-like growth factor 1 stimulation or exercise training. In contrast, Akt1 activity was found to antagonize pathologic cardiac growth that occurs in response to endothelin 1 stimulation or pressure overload. Evaluation of an Akt2-deficient mouse model system demonstrated that this family member plays an important role in insulin-stimulated glucose uptake and metabolism, and may not regulate physiologic or pathologic cardiac growth. Therefore, Akt1 selectively promotes physiological cardiac growth while Akt2 selectively promotes insulin-stimulated cardiac glucose metabolism.
Muslin
Anthony J
AJ
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
DeBosch
Brian
B
D000818:Animals; D002468:Cell Physiological Phenomena; D049109:Cell Proliferation; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt