title: Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.
abstract: Skeletal muscle is a heterogeneous tissue composed of different fiber types. Studies suggest that insulin-mediated glucose metabolism is different between muscle fiber types. We hypothesized that differences are due to fiber type-specific 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-E1α (PDH-E1α) 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-E1α). 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-E1α) 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.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Albers
authors.affiliation: Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark.
authors.forename: Andreas J T
authors.initials: AJ
authors.lastname: Pedersen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Birk
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Dorte E
authors.initials: DE
authors.lastname: Kristensen
authors.affiliation: Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark.
authors.forename: Birgitte F
authors.initials: BF
authors.lastname: Vind
authors.affiliation: Section of Biology, Department of Oral Function and Molecular Biology, School of Dentistry, Ohu University, Koriyama, Japan.
authors.forename: Otto
authors.initials: O
authors.lastname: Baba
authors.affiliation: Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Jane
authors.initials: J
authors.lastname: Nøhr
authors.affiliation: Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark.
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark jwojtaszewski@nexs.ku.dk.
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007328:Insulin