Use of GLUT-4 null mice to study skeletal muscle glucose uptake.

1. The present review focuses on the effects of varying levels of GLUT-4, the insulin-sensitive glucose transporter, on insulin sensitivity and whole body glucose homeostasis. 2. Three mouse models are discussed including myosin light chain (MLC)-GLUT-4 mice which overexpress GLUT-4 specifically in skeletal muscle, GLUT-4 null mice which express no GLUT-4 and the MLC-GLUT-4 null mice which express GLUT-4 only in skeletal muscle. Overexpressing GLUT-4 specifically in the skeletal muscle results in increased insulin sensitivity in the MLC-GLUT-4 mice. In contrast, the GLUT-4 null mice exhibit insulin intolerance accompanied by abnormalities in glucose and lipid metabolism. Restoring GLUT-4 expression in skeletal muscle in the MLC-GLUT-4 null mice results in normal glucose metabolism but continued abnormal lipid metabolism. 3. The results of experiments using these mouse models demonstrates that modifying the expression of GLUT-4 profoundly affects whole body insulin action and consequently glucose and lipid metabolism.