Subcellular trafficking of GLUT4 in insulin target cells

Abstract

Abstract Insulin stimulates glucose transport in its target tissues primarily by inducing a translocation of GLUT4 from intracellular membranes to the plasma membrane. The kinetics of subcellular trafficking of GLUT4 between these compartments have been investigated using a bis-mannose photolabel. Since this reagent is impermeant, it has been used to selectively tag cell surface GLUT4. Subsequent examination of the changes in distribution of the tagged transporter allows resolution of the sites of insulin action in the subcellular trafficking pathway. This approach indicates that insulin mainly increases the rate constant for exocytosis of GLUT4. In addition, these kinetic studies have lead to the suggestion that GLUT4 trafficks through at least two intracellular compartments during its cycling and that an occluded plasma membrane compartment may be an intermediate in insulin-stimulated exocytosis. Some of the key proteins that catalyse the vesicle trafficking steps are now being resolved. Phosphatidylinositol 3-kinase may have a regulatory role in GLUT4 vesicle budding and fission at several intracellular membrane sites while the N-ethylmaleimide sensitive fusion protein (NSF) complex may have a role in regulation of GLUT4 vesicle docking and fusion at the plasma membrane.