Glucose enters eucaryotic cells via 2 different types of membrane associated
carrier proteins, the Na+-coupled
glucose transporters (SGLT) and
glucose transporter facilitators (GLUT). Three members of the SGLT family function as
sugar transporters (SGLT1 and SGLT2) or sensors (SGLT3). The human GLUT family consists of 14 members, of which 11 have been shown to catalyze
sugar transport. The individual isotypes exhibit different substrate specificity, kinetic characteristics, and expression profiles, thereby allowing a tissue-specific adaptation of
glucose uptake through regulation of their gene expression. Furthermore, some transporters (eg, GLUT4 and GLUT8) are regulated by their subcellular distribution. In addition to catalyzing
glucose entry into cells, some isotypes (eg, GLUT2) seem to be involved in the mechanisms of glucosensing of pancreatic beta-cells, neuronal, or other cells, thereby playing a major role in the hormonal and neural control. Targeted disruption in mice has helped to elucidate the physiologic function of some isotypes (GLUT1, GLUT2, GLUT4). Furthermore, several
congenital defects of
sugar metabolism are caused by aberrant transporter genes (eg, the
glucose-galactose malabsorption syndrome, SGLT1; the
glucose transporter 1 deficiency syndrome; and the
Fanconi-Bickel syndrome, GLUT2). In addition, a malfunction of
glucose transporter expression or regulation (GLUT4) appears to contribute to the
insulin resistance syndrome.