1. The present review focuses on the effects of varying levels of GLUT‐4, the insulin‐senstive 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 skleletal 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 expresssion of GLUT‐4 profoundly affects whole body insulin action and consequently glucose and lipid metabolism.