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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 \u00b1 the GLUT1 inhibitor BAY-876. [3H]-hexose uptake \u00b1 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 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/biom12121734","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:10:54Z","timestamp":1669169454000},"page":"1734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-8747","authenticated-orcid":false,"given":"Shawna L.","family":"McMillin","sequence":"first","affiliation":[{"name":"Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parker L.","family":"Evans","sequence":"additional","affiliation":[{"name":"Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William M.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke A.","family":"Weyrauch","sequence":"additional","affiliation":[{"name":"Departments of Kinesiology, Biochemistry & Molecular Biology, and Physiology, Brody School of Medicine, East Carolina Diabetes & Obesity Institute, East Carolina University, Greenville, NC 27858, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler J.","family":"Sermersheim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, and Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Indiana Center for Diabetes & Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2353-0325","authenticated-orcid":false,"given":"Steven S.","family":"Welc","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology & Physiology, and Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique R.","family":"Heitmeier","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Hresko","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-3355","authenticated-orcid":false,"given":"Paul W.","family":"Hruz","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9029-3390","authenticated-orcid":false,"given":"Francoise","family":"Koumanov","sequence":"additional","affiliation":[{"name":"Department of Health, University of Bath, Bath BA2 7AY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey D.","family":"Holman","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-0738","authenticated-orcid":false,"given":"E. 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