We previously reported that insulin induces the translocation of GLUT4 to both the plasma membrane and the transverse tubules (T-tubules) in rat skeletal muscle {Am J Physiol 270:E667–E676, 1996). The aim of the present study was to investigate whether the insulin-resistant glucose utilization of skeletal muscle from streptozotocin (STZ)-induced diabetic rats is linked to an impaired translocation of GLUT4 to the plasma membrane, the T-tubules, or both surface compartments. Whole-body insulin-mediated glucose disposal, assessed during a hyperinsulinemic-euglycemic clamp, was reduced by 48% (P < 0.01) in diabetic rats as compared with controls. Subcellular membrane fractions enriched with plasma membranes, T-tubules, or GLUT4-enriched intracellular membranes were isolated from hindlimb muscles of control and insulinstimulated rats, and GLUT4 content was measured by Western blot analysis. In the absence of insulin (unstimulated), GLUT4 content in muscle of diabetic rats was markedly lower (by ∼40%) in both the Ttubules and the intracellular membrane fraction as compared with controls. In contrast, the transporter protein levels were similar in the plasma membrane fraction. In skeletal muscle of control animals, the hyperinsulinemic clamp induced GLUT4 translocation from the intracellular membrane pool to both the plasma membrane and the T-tubule-enriched fractions (∼2.2-fold to ∼2.5-fold). Surprisingly, insulin increased plasma membrane GLUT4 content to comparable levels in control and diabetic rat skeletal muscle. However, insulin-mediated GLUT4 translocation to the T-tubules was significantly reduced in the same muscle. Wholebody insulin action was significantly correlated with GLUT4 protein levels in the T-tubules, but not with the transporter content in either plasma membranes or intracellular membranes. These results strongly suggest that peripheral resistance to insulin action on glucose disposal inSTZ-induced diabetic rats is caused by a selective impairment of GLUT4 translocation to skeletal muscle T-tubules.
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Metabolism and Signal Transduction|
January 01 1998
Selective Impairment in GLUT4 Translocation to Transverse Tubules in Skeletal Muscle of Streptozotocin-Induced Diabetic Rats
Luce Dombrowski;
Luce Dombrowski
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center
Ste-Foy, Québec, Canada
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Denis Roy;
Denis Roy
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center
Ste-Foy, Québec, Canada
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André Marette
André Marette
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center
Ste-Foy, Québec, Canada
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Address correspondence and reprint requests to Dr. André Marette, Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, 2705 Laurier Blvd., Ste-Foy, Québec, Canada G1V 4G2. E-mail: [email protected]
Diabetes 1998;47(1):5–12
Article history
Received:
February 20 1997
Revision Received:
September 10 1997
Accepted:
September 10 1997
PubMed:
9421368
Citation
Luce Dombrowski, Denis Roy, André Marette; Selective Impairment in GLUT4 Translocation to Transverse Tubules in Skeletal Muscle of Streptozotocin-Induced Diabetic Rats. Diabetes 1 January 1998; 47 (1): 5–12. https://doi.org/10.2337/diab.47.1.5
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