Insulin-stimulated glucose uptake in skeletal muscle is mediated through the GLUT4 glucose transporter. Transgenic (TG) mice overexpressing human GLUT4 in skeletal muscle show an increased ability to handle a glucose load. Here, the participation of the overexpressed GLUT4 in the response to insulin was examined. In TG mouse muscle, the GLUT4 protein content was 10-fold higher in crude membrane (CM), sevenfold higher in internal membrane (IM), and 15-fold higher in a plasma membrane (PM)-rich fraction, relative to non-TG littermates. This suggested partial saturation of the normal sorting mechanisms. The distribution and abundance of the GLUT1 glucose transporter was not affected. Insulin injection (4.3 U/kg body wt) increased GLUT4 in the PM-rich fraction; the increase was threefold higher in TG than in non-TG mice. Insulin decreased the GLUT4 content of the IM in both animal groups and of a second, heavier intracellular membrane fraction only in TG mice. The net content of Na+-K+-pump subunits was 40–65% lower in CM from TG compared with non-TG littermates. In spite of this, insulin caused a three- to sixfold higher translocation of the α2 and β1 subunits of the Na+-K+-pump in TG compared with non-TG animals. The results suggest that overexpression of GLUT4 confers to the muscle increased ability to translocate subunits of the Na+-K+-pump either as a direct consequence of the recruitment of glucose transporters or as an adaptation to the more demanding metabolic state.
Muscle Subcellular Localization and Recruitment by Insulin of Glucose Transporters and Na+-K+-ATPase Subunits in Transgenic Mice Overexpressing the GLUT4 Glucose Transporter
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Toolsie Ramlal, H Stephen Ewart, Romel Somwar, Rhonda O Deems, Michele A Valentin, Douglas A Young, Amira Klip; Muscle Subcellular Localization and Recruitment by Insulin of Glucose Transporters and Na+-K+-ATPase Subunits in Transgenic Mice Overexpressing the GLUT4 Glucose Transporter. Diabetes 1 November 1996; 45 (11): 1516–1523. https://doi.org/10.2337/diab.45.11.1516
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