Chapter 2 Facilitative glucose transport

Abstract

The precise regulation of absorption and distribution of glucose and other sugars in mammals is carried out by two families of proteins, the Na + -dependent glucose transporter and the family of facilitative glucose transporters. The six functional members of the facilitative transporters, GLUT1 through GLUT5 and GLUT7 have distinct but overlapping tissue distributions and are targeted to distinct subcellular locales in the cell types in which they are expressed. The distinct kinetic properties and substrate selectivity of each of the transporters have evolved such that efficient fuel delivery to appropriate tissues is ensured under a wide variety of metabolic conditions. The primary, secondary, and presumably tertiary, and higher, structure of the family of facilitative glucose transporters are similar. It is beginning to be under-stood which domains of these transporters are important for substrate and inhibitor binding and for subcellular localization. Future work will undoubtably uncover the molecular mechanism by which the facilitative transporters catalyze the translocation of sugars across the membrane. Also becoming clear is the mechanism by which the levels and activity of the glucose transporters change in response to altered homeostasis, such as insulin-dependent and noninsulin-dependent diabetes mellitus and other insulin resistant states. It will be appreciated which changes in transporter levels are a proximal event in altering normal physiology, such as changes in GLUT2 in the β-cell of the islets of Langerhans or in the small intestine with alternative diets, and which are due to the altered metabolic states such as diabetes or uremia but could exacerbate the pathophysiology seen.