The most important findings of our study are (1) that silencing of UCP-2 in cultured adult rat ventricular cardiomyocytes improves glucose uptake and preserves cell function in an Ang II-driven model of cell dysfunction, (2) that UCP-2 expression is transiently down- and glucose uptake clearly up-regulated during the adaptive phase of cardiac hypertrophy, but (3) that an up-regulation of UCP-2 at the time of decompensation is associated with less Glut-4 expression and reduced function. The gene discussed is UCP2; the disease is cardiac hypertrophy.