In muscle and adipose cells, insulin stimulates glucose uptake more than several folds by recruiting the insulin-regulated glucose transporter, GLUT4 from intracellular compartments to the plasma membrane. While such large insulin stimulation of glucose transport coincides with the expression of GLUT4 during differentiation of these cells, GLUT4 expression does not necessarily confer insulin sensitivity to glucose transport in other types of cells. Previous studies have shown that in muscle and adipose cells, GLUT4 is targeted to a unique GLUT4 storage compartment (GSC) sequestered from the constitutive recycling pathway, whereas the significance and the mechanism of GLUT4 targeting to GSC have remained obscure. We have recently found that Ubc9, the SUMO conjugating enzyme, may be an important regulatory protein in subcellular targeting and turnover of GLUT4. Adenovirus vector-mediated overexpression of Ubc9 in 3T3-L1 adipocytes substantially increased GLUT4, which was accompanied by promoted targeting of GLUT4 to GSC, consequently leading to enhanced insulin responsiveness of glucose transport. On the other hand, siRNA-mediated depletion of Ubc9 caused a marked down-regulation of GLUT4, with a selective loss of GLUT4 in GSC, and significantly attenuated the insulin effect on glucose transport. Interestingly, the turnover of GLUT4 was significantly retarded by targeting to GSC, but was accelerated by residing in the recycling pathway. Thus, Ubc9 plays an indispensable role in acquisition and maintenance of the insulin sensitivity of glucose transport in adipocytes. [J Physiol Sci. 2006;56 Suppl:S18]
