Preservation of glucose metabolism in hypertrophic GLUT4-null hearts

GLUT4-null mice lacking the insulin-sensitive glucose transporter are not d iabetic but do exhibit abnormalities in glucose and lipid metabolism. The m ost striking morphological consequence of ablating GLUT4 is cardiac hypertr ophy. GLUT4-null hearts display characteristics of hypertrophy caused by hy pertension. However, GLUT4-null mice have normal blood pressure and maintai n a normal cardiac contractile protein profile. Unexpectedly, although they lack the predominant glucose transporter in the heart, GLUT4-null hearts t ransport glucose and synthesize glycogen at normal levels, but gene express ion of rate-limiting enzymes involved in fatty acid oxidation is decreased. The GLUT4-null heart represents a unique model of hypertrophy that may be used to study the consequences of altered substrate utilization in normal a nd pathophysiological conditions.