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 Hruz, Francoise Koumanov, Geoffrey D. Holman, E. Dale Abel, Carol A. Witczak

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number1734
JournalBiomolecules
Volume12
Issue number12
DOIs
Publication statusPublished - 23 Nov 2022

Keywords

  • GLUT1
  • synergist ablation
  • BAY-876
  • bio-LC-ATB-BGPA
  • glucose transport
  • SLC2A1
  • mechanical overload
  • skeletal muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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