Activation of Akt is strongly associated with hypertrophic cardiac growth; while adaptive in the short-term, persistent stimulation of Akt signaling is deleterious due to feedback inhibition of insulin receptor substrate, PI3K signaling, and GLUT4-mediated glucose uptake, and may help precipitate heart failure due to a mismatch between cardiac hypertrophy and angiogenesis [Figure 4][255–257]. The gene discussed is AKT1; the disease is heart failure.