The facilitative glucose transporter and insulin action

Cellular uptake of glucose is a tightly controlled process, It is mediated by a family of intrinsic membrane proteins (facilitated glucose transporters or GLUTs), and further regulated by metabolites and hormones, By far the most important GLUT regulation in human physiology is that by insulin, dysfunction of which may produce insulin resistance, a hallmark of diabetes mellitus and obesity, Six isoforms are now known in GLUT family, They differ in tissue-specific expression and regulation, yet share a common transmembrane topology showing a highly conserved transmembrane domain, and less conserved cytoplasmic and exoplasmic domains, Evidence indicates that the transmembrane domain accommodates a water-filled glucose pathway (the catalytic domain), Little is known about the role of the exoplasmic domain. As for the cytoplasmic domain, a large body of evidence indicates its importance in tissue-specific regulation of GLUT function (the regulatory domain), This domain includes the N-terminal segment, the large, central loop, and the C-terminal segment. Exactly how this domain participates in GLUT regulation is not known. An interesting possibility is that the regulation involves a specific cellular protein, which interacts with GLUT at the cytoplasmic domain and modulates the function, This putative, glucose transporter binding protein (GTBP) may be an enzyme, or a nonenzymatic adaptor or docking protein, Indeed, we have identified several cytosolic proteins that bind to the cytoplasmic domain of GLUT proteins; these include glyceraldehyde-3-phosphate dehydrogenase, glucokinase, GTBP70, GTBP85, GTBP28, and L-3-hydroxyacyl CoA dehydrogenase. Interaction of GLUT protein with some of these GTPBs are functionally coupled, Whether any of these interactions is actually responsible for the insulin-induced GLUT regulation is yet to be determined.