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.