GLUT4 gene regulation and manipulation

A decade has passed since the cloning of the insulin-responsive glucose transporter, GLUT4. Numerous studies have demonstrated the complex hormonal and metabolic regulation of GLUT4 gene expression in adipose tissue and muscle. Careful dissection of the regulatory elements in the GLUT4 promoter has provided insight into the intricate control of this central gene of glucose homeostasis. Genetic manipulation of mice has provided further insight into the role of GLUT4 in carbohydrate and lipid metabolism at the whole body and tissue- specific levels. Analysis of GLUT4+/-, GLUT4 null, and muscle- complemented GLUT4 knockout mice has furthered our understanding of peripheral insulin sensitivity. Additional studies on GLUT4 gene regulation and GLUT4 knockout models are likely to lead to novel therapies for type II diabetes and other diseases of insulin resistance.