The GLUTs Family - Lessons from Transgenic Mice

The glucose transporters (GLUTs) are currently a 13 member family of facilitative transmembrane proteins which transport glucose down its concentration gradient. The GLUTs have a tissue specific expression and regulation. Dysregulation of GLUTs have been implicated in the pathogenesis of a number of diseases including diabetes and cancer and are known to play an important role in the developing embryo. In addition, roles for GLUTs in cardiac function and embryonic development have been identified and will be discussed in this review. The ability to ablate or over-express GLUTs has advanced our understanding of the role these transporters play in the maintenance of normal glucose homeostasis and the pathogenesis of diabetes. The development of Cre-LoxP technology coupled with the existence of tissue specific promoters allows investigators to manipulate gene expression both globally and in a tissue specific manner. The major GLUTs which have been investigated using transgenic technology are GLUT1, GLUT4 and GLUT2. Overexpression of GLUT4 and GLUT1 results in increased glucose uptake and metabolism. However, only GLUT4 overexpression protects against the development of insulin resistance in transgenic mice. Genetic ablation of GLUT4 and GLUT2 results in impaired insulin tolerance and defects in both lipid and glucose metabolism. This review will present various transgenic models of GLUT modification and discuss what has been learned from these models about the role that GLUTs play in glucose homeostasis, insulin action and development.