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 subcellul ar content of GLUT4 in diabetic rat muscle, and to test the hypothesis that a reduced abundance of the transporter protein in transverse tub ules is responsible for impaired glucose utilization in that tissue. G LUT4 protein levels were measured in hindlimb muscle homogenates as we ll as in subcellular membrane fractions enriched with either plasma me mbranes, transverse tubules, or GLUT4-containing intracellular membran es from control and diabetic (streptozotocin-induced) rats. GLUT4 prot ein contents in diabetic muscle homogenates was reduced by 30% as comp ared to control rats. Subcellular fractionation experiments revealed t hat GLUT4 contents in transverse tubules-enriched fractions was marked ly decreased (by 55-60%) in skeletal muscle of diabetic animals wherea s no significant reductions in GLUT4 abundance was observed in the pla sma membrane fraction, Moreover, GLUT4 was markedly depleted (by 45%) in the GLUT4-enriched intracellular membrane fraction. These results i ndicate that GLUT4 is markedly depleted in both the intracellular pool and in the cell surface membranes in muscle of STZ-diabetic rats. Mos t strikingly, this study demonstrates that transverse tubules and not the plasma membrane are the main sites of cell surface GLUT4 depletion in diabetic muscle.