Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes
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Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes. / Albers, Peter Hjorth; Pedersen, Andreas J T; Birk, Jesper Bratz; Kristensen, Dorte Enggaard; Vind, Birgitte F; Baba, Otto; Nøhr, Jane; Højlund, Kurt; Wojtaszewski, Jørgen.
I: Diabetes, Bind 64, Nr. 2, 2015, s. 485-497.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes
AU - Albers, Peter Hjorth
AU - Pedersen, Andreas J T
AU - Birk, Jesper Bratz
AU - Kristensen, Dorte Enggaard
AU - Vind, Birgitte F
AU - Baba, Otto
AU - Nøhr, Jane
AU - Højlund, Kurt
AU - Wojtaszewski, Jørgen
N1 - CURIS 2015 NEXS 051
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.2337/db14-0590
DO - 10.2337/db14-0590
M3 - Journal article
C2 - 25187364
VL - 64
SP - 485
EP - 497
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 2
ER -
ID: 123269383