1 Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet2 PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet3 Diabetes Research Center, Department of Endocrinology, Odense University Hospital, Odense, Denmark.4 Section of Biology, Department of Oral Function & Molecular Biology, School of Dentistry, Ohu University, Koriyama, Japan.5 Novo Nordisk A/S (Biz)6 PhD, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet7 Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
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 to type II fibers have higher protein levels of the insulin receptor, GLUT4, hexokinase II, glycogen synthase (GS), pyruvate dehydrogenase (PDH-E1α) and a lower protein content of Akt2, TBC1D4 and TBC1D1. In type I fibers compared to 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 to lean and obese subjects. We conclude that human type I muscle fibers compared to type II fibers have a higher glucose handling capacity but a similar sensitivity for phosphor-regulation by insulin.