ABSTRACT
Corresponding Author: Maureen J.Charron Phone: 718-430-2852; Fax: 718-4308676; Email: charron@aecom.yu.edu
SUMMARY
Regulation of plasma glucose levels is of central importance in health since all mammalian cells use glucose as a source of energy and as a precursor for synthesis of other carbon-containing compounds in the organism. Maintenance of normal glucose homeostasis results from the integration of three processes: glucose absorption from the gut, production of glucose by the liver in the fasting state and glucose utilization by almost all tissues in the body (DeFronzo et al., 1991). This balance is maintained through the action of hormones (insulin and glucagon) and by family of facilitative glucose transporters that are responsible for glucose entry into the cells. The leading role in maintaining glucose homeostasis is played by muscle because it is the major site of insulin stimulated glucose disposal (DeFronzo et al., 1988, Shulman et al., 1990). The main facilitative glucose transporter in the skeletal muscle and cardiac muscle, as well as adipose tissue is the GLUT4 isoform. (for review Birnbaum et al., 1997). The results of genetic manipulations of mice leading to the alterations in the expression of GLUT4 proved that GLUT4 is a primary target for insulin-mediated glucose disposal. General or tissue specific overexpression of the GLUT4 gene resulted in improved insulin responsiveness and peripheral glucose utilization (Katz et al., 1996). Moreover, several studies demonstrated that GLUT4 expression, translocation and/or activity are decreased in animals exhibiting an insulin resistant phenotype (Kahn et al., 1992; for review Stephens et al., 1995). GLUT4 is unique in the manner in which it facilitates the delivery of glucose to the tissues where it is expressed. It is translocated from its intracellular pool to the plasma membrane under the influence of insulin or other modes of stimulation ie: hypoxia and contraction (for review Goodyear et al., 1998). Thus, glucose transport,
especially that of skeletal muscle, is the rate limiting step involved in glucose metabolism and plays a crucial role in the maintenance of whole body glycemia (DeFronzo et al., 1988; Shulman et al., 1990; Ziel et al., 1988; Ren et al., 1993).
