To be or not to be: Regulation of the Intrinsic Activity of GLUT4

Abstract

Insulin increases the rate of glucose uptake into muscle and fat cells. Numerous studies provide evidence that this is accomplished through an increase in the cell-surface amount of the facilitative glucose transporter GLUT4. Diverse techniques have been used to document a time-dependent gain in surface GLUT4, often in conjunction with a decrease in its intracellular content. These include subcellular fractionation coupled to immunoblotting, affinity photolabelling coupled to immunoprecipitation, and surface detection by immunofluorescence and immunoelectron microscopy. However, there are also abundant reports of a discrepancy between the extent of stimulation of the rate of glucose uptake by insulin and the increase in the amount of cell-surface transporters. One interpretation of this discrepancy is that insulin regulates the intrinsic activity of GLUT4 in addition to recruiting transporters to the cell surface. Several interpretations of this discrepancy can be offered, based on the experimental techniques used to measure glucose uptake and cell-surface GLUT4. Here we discuss the methods used to quantify these observations. Subsequently, we inspect the studies that have measured the insulin-stimulated increase in cell-surface GLUT4 concurrently with glucose uptake, in order to determine if there is realistic evidence to support the hypothesis that insulin regulates GLUT4 intrinsic activity. We conclude that in spite of various possible explanations for the discrepancy between the stimulation of glucose uptake and that of cell surface GLUT4, there is solid evidence to suggest that insulin increases the intrinsic activity of GLUT4. Keywords: insulin, glucose transporters (gluts), expression, translocation, plasma membrane (pm)