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Myostatin reduces insulin‐stimulated phosphorylation of AS160 in human skeletal muscle cells
Author(s) -
Consitt Leslie,
Gallagher Sean
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb810
Subject(s) - myostatin , insulin resistance , medicine , endocrinology , skeletal muscle , myogenesis , insulin receptor , biology , myokine , insulin , glucose uptake , phosphorylation , signal transduction , microbiology and biotechnology
Skeletal muscle insulin resistance is a characteristic feature of type 2 diabetes and plays a prominent role in the development of this disease. Despite this knowledge, the cellular mechanism(s) contributing to insulin resistance remain unknown. Myostatin, a member of the transforming growth factor‐β (TGF‐β) superfamily has been linked to insulin resistance; however, the cellular role of myostatin‐induced insulin resistance in skeletal muscle remains to be elucidated. The purpose of the present study was to 1) identify myostatin‐mediated pathways and 2) determine the role of myostatin in distal insulin signaling (AS160) in human skeletal muscle cells. Human myotubes were incubated with myostatin (100 ng/mL) for up to 24 hours. Myostatin incubation of myotubes resulted in the rapid (5–20 min) phosphorylation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2), p38 MAPK, c‐Jun NH2‐terminal kinase (JNK), and mothers against decapentaplegic homolog 2 (SMAD2). In response to insulin, phosphorylation of AS160‐Thr642 declined 23% (P<0.05) after chronic (24 hour) myostatin incubation. In addition, intramyocellular lipid (IMCL) content increased 29%, (P<0.01) in response to 24 hour myostatin incubation. These data demonstrate that myostatin stimulates a number of intracellular metabolic pathways in human skeletal muscle and suggests this protein may contribute to the accumulation of IMCL and insulin resistance.