Marked depletion of GLUT4 glucose transporters in transverse tubules of skeletal muscle from streptozotocin-induced diabetic rats.

The principal goal of the present study was to determine the subcellular content of GLUT4 in diabetic rat muscle, and to test the hypothesis that a reduced abundance of the transporter protein in transverse tubules is responsible for impaired glucose utilization in that tissue. GLUT4 protein levels were measured in hindlimb muscle homogenates as well as in subcellular membrane fractions enriched with either plasma membranes, transverse tubules, or GLUT4-containing intracellular membranes from control and diabetic (streptozotocin-induced) rats. GLUT4 protein contents in diabetic muscle homogenates was reduced by 30% as compared to control rats. Subcellular fractionation experiments revealed that GLUT4 contents in transverse tubules-enriched fractions was markedly decreased (by 55-60%) in skeletal muscle of diabetic animals whereas no significant reductions in GLUT4 abundance was observed in the plasma membrane fraction. Moreover, GLUT4 was markedly depleted (by 45%) in the GLUT4-enriched intracellular membrane fraction. These results indicate that GLUT4 is markedly depleted in both the intracellular pool and in the cell surface membranes in muscle of STZ-diabetic rats. Most strikingly, this study demonstrates that transverse tubules and not the plasma membrane are the main sites of cell surface GLUT4 depletion in diabetic muscle.