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Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type\u2013specific expression\/regulation of insulin signaling elements and\/or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese, and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared with type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), and pyruvate dehydrogenase-E1\u03b1 (PDH-E1\u03b1) and a lower protein content of Akt2, TBC1 domain family member 4 (TBC1D4), and TBC1D1. In type I fibers compared with type II fibers, the phosphorylation response to insulin was similar (TBC1D4, TBC1D1, and GS) or decreased (Akt and PDH-E1\u03b1). Phosphorylation responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS, and PDH-E1\u03b1) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared with lean and obese subjects. We conclude that human type I muscle fibers compared with type II fibers have a higher glucose-handling capacity but a similar sensitivity for phosphoregulation by insulin.<\/jats:p>","DOI":"10.2337\/db14-0590","type":"journal-article","created":{"date-parts":[[2014,9,4]],"date-time":"2014-09-04T14:16:25Z","timestamp":1409840185000},"page":"485-497","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":190,"title":["Human Muscle Fiber Type\u2013Specific Insulin Signaling: Impact of Obesity and Type 2 Diabetes"],"prefix":"10.2337","volume":"64","author":[{"given":"Peter H.","family":"Albers","sequence":"first","affiliation":[{"name":"Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark"},{"name":"Diabetes Research Unit, Novo Nordisk A\/S, Maaloev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J.T.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper B.","family":"Birk","sequence":"additional","affiliation":[{"name":"Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorte E.","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte F.","family":"Vind","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Baba","sequence":"additional","affiliation":[{"name":"Section of Biology, Department of Oral Function and Molecular Biology, School of Dentistry, Ohu University, Koriyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"N\u00f8hr","sequence":"additional","affiliation":[{"name":"Diabetes Research Unit, Novo Nordisk A\/S, Maaloev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"H\u00f8jlund","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen F.P.","family":"Wojtaszewski","sequence":"additional","affiliation":[{"name":"Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,9,3]]},"reference":[{"key":"2022031223150982200_B1","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.2337\/diab.30.12.1000","article-title":"The effect of insulin on the disposal of intravenous glucose. 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