Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake
Shawna L. McMillin,
Parker L. Evans,
William M. Taylor,
Luke A. Weyrauch,
Tyler J. Sermersheim,
Steven S. Welc,
Monique R. Heitmeier,
Richard C. Hresko,
Paul W. Hruz,
Francoise Koumanov,
Geoffrey D. Holman,
E. Dale Abel,
Carol A. Witczak
Affiliations
Shawna L. McMillin
Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA
Parker L. Evans
Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA
William M. Taylor
Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA
Luke A. Weyrauch
Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA
Tyler J. Sermersheim
Department of Anatomy, Cell Biology & Physiology, and Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Steven S. Welc
Department of Anatomy, Cell Biology & Physiology, and Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Monique R. Heitmeier
Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA
Richard C. Hresko
Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA
Paul W. Hruz
Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA
Francoise Koumanov
Department of Health, University of Bath, Bath BA2 7AY, UK
Geoffrey D. Holman
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
E. Dale Abel
Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology & Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Carol A. Witczak
Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA
Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [3H]-2-deoxyglucose uptake ± the GLUT1 inhibitor BAY-876. [3H]-hexose uptake ± BAY-876 was also examined in HEK293 cells-expressing GLUT1-6 or GLUT10. mGLUT1KO mice exhibited no impairments in body weight, lean mass, whole body metabolism, glucose tolerance, basal or overload-stimulated muscle glucose uptake. There was no compensation by the insulin-responsive GLUT4. In mGLUT1KO mouse muscles, overload stimulated higher expression of mechanosensitive GLUT6, but not GLUT3 or GLUT10. In control and mGLUT1KO mouse muscles, 0.05 µM BAY-876 impaired overload-stimulated, but not basal glucose uptake. In the GLUT-HEK293 cells, BAY-876 inhibited glucose uptake via GLUT1, GLUT3, GLUT4, GLUT6, and GLUT10. Collectively, these findings demonstrate that GLUT1 does not mediate basal muscle glucose uptake and suggest that a novel glucose transport mechanism mediates overload-stimulated glucose uptake.
