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.
Skip Nav Destination
Article navigation
Original Articles|
November 01 1996
Muscle Subcellular Localization and Recruitment by Insulin of Glucose Transporters and Na+-K+-ATPase Subunits in Transgenic Mice Overexpressing the GLUT4 Glucose Transporter
Toolsie Ramlal;
Toolsie Ramlal
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
H Stephen Ewart;
H Stephen Ewart
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Romel Somwar;
Romel Somwar
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Rhonda O Deems;
Rhonda O Deems
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Michele A Valentin;
Michele A Valentin
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Douglas A Young;
Douglas A Young
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Amira Klip
Amira Klip
Division of Cell Biology, The Hospital for Sick Children
Toronto, Ontario, Canada
Metabolic Diseases Department, Preclinical Research, Sandoz Research Institute
East Hanover
Metabolism, Bristol-Myers Squibb
Princeton, New Jersey
Search for other works by this author on:
Address correspondence and reprint requests to Dr. Amira Klip, Division of Cell Biology, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada.
Diabetes 1996;45(11):1516–1523
Article history
Received:
February 08 1996
Revision Received:
June 06 1996
Accepted:
June 06 1996
PubMed:
8866555
Citation
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
Download citation file:
53
Views