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 language||English (US)|
|State||Published - Dec 2022|
Bibliographical noteFunding Information:
This research was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, grant number F31-DK119080 (S.L.M.), grant number R01-DK103562 (C.A.W.); the Medical Research Council (UK), grant number MR/P002927/1 (F.K.); the Children’s Discovery Institute, grant number MI-II-2017-593, (P.W.H.); and by the American College of Sports Medicine Foundation, grant number 18-00636 (S.L.M.); and the Muscular Dystrophy Association, grant number 603201 (S.S.W). Additional support was provided by the Indiana University School of Medicine and the Indiana Center for Musculoskeletal Health as new laboratory start-up funds to S.S.W. and C.A.W.
© 2022 by the authors.
- glucose transport
- mechanical overload
- skeletal muscle
- synergist ablation
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't