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Diabetes. 2015 Feb;64(2):485-97. doi: 10.2337/db14-0590. Epub 2014 Sep 3.

Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.

Author information

1
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.
2
Department of Endocrinology, Diabetes Research Center, Odense University Hospital, Odense, Denmark.
3
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
4
Section of Biology, Department of Oral Function and Molecular Biology, School of Dentistry, Ohu University, Koriyama, Japan.
5
Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark.
6
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark jwojtaszewski@nexs.ku.dk.

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.

PMID:
25187364
DOI:
10.2337/db14-0590
[Indexed for MEDLINE]
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