Insulin stimulates the entry of GLUT4 into the endosomal recycling pathway by a quantal mechanism

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Adelle C F CosterD E James

Abstract

The insulin-sensitive glucose transporter GLUT4 mediates the uptake of glucose into adipocytes and muscle cells. In this study we have used a novel 96-well plate fluorescence assay to study the kinetics of GLUT4 trafficking in 3T3-L1 adipocytes. We have found evidence for a graded release mechanism whereby GLUT4 is released into the plasma membrane recycling system in a nonkinetic manner as follows: the kinetics of appearance of GLUT4 at the plasma membrane is independent of the insulin concentration; a large proportion of GLUT4 molecules do not participate in plasma membrane recycling in the absence of insulin; and with increasing insulin there is an incremental increase in the total number of GLUT4 molecules participating in the recycling pathway rather than simply an increased rate of recycling. We propose a model whereby GLUT4 is stored in a compartment that is disengaged from the plasma membrane recycling system in the basal state. In response to insulin, GLUT4 is quantally released from this compartment in a pulsatile manner, leaving some sequestered from the recycling pathway even in conditions of excess insulin. Once disengaged from this location we suggest that in the continuous presence of insulin this quanta of GLUT4...Continue Reading

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Citations

Aug 30, 2008·The Journal of Membrane Biology·Jelena VelebitRobert Zorec
Mar 17, 2011·Biochemistry·Kevin FoleyAmira Klip
Nov 17, 2009·The Journal of Biological Chemistry·Daniel J FazakerleyAdelle C F Coster
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