McMillin, Shawna L.Evans, Parker L.Taylor, William M.Weyrauch, Luke A.Sermersheim, Tyler J.Welc, Steven S.Heitmeier, Monique R.Hresko, Richard C.Hruz, Paul W.Koumanov, FrancoisHolman, Geoffrey D.Abel, E. DaleWitczak, Carol A.2023-10-022023-10-022022-11-23McMillin SL, Evans PL, Taylor WM, et al. Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake. Biomolecules. 2022;12(12):1734. Published 2022 Nov 23. doi:10.3390/biom12121734https://hdl.handle.net/1805/35937Glucose 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.en-USAttribution 4.0 InternationalBAY-876GLUT1SLC2A1bio-LC-ATB-BGPAGlucose transportMechanical overloadSkeletal muscleSynergist ablationArticle