Insulin-like growth factor I-mediated skeletal muscle hypertrophy is characterized by increased mTOR-p70S6K signaling without increased Akt phosphorylation.

摘要: Background Insulin-like growth factor I (IGF-I) is an anabolic hormone that known to induce skeletal muscle hypertrophy. However, the signaling pathways mediating IGF-I9s hypertrophic effect in vivo are unknown. Method The phosphorylation of 46 proteins was investigated by Kinetworks proteomic analysis gastrocnemius transgenic mice overexpressing IGF-I myosin light chain/muscle specific (MLC/mIgf-I) and wild-type littermates. Results In MLC/mIgf-I mice, we observed increased phosphoinositide-dependent protein kinase 1 (PDK1; 53% increase), mammalian target rapamycin (mTOR; 112% p70 S6 (p70S6K) (254% increase) but no significant change Akt (4% decrease). Furthermore, found reduced MAP 2 (MEK1/2) (60% decrease) mitogen-activated kinases 3 6 (MKK3/6) (50% from suggesting mitogenic effects mediated via distinct inhibition (MAP) pathway may be required for IGF-I-induced effect. Single-fiber revealed a trend toward higher percentage fast twitch fibers (IIb IIx) mice. Conclusion Persistent overexpression results hypertrophy, which likely mTOR/p70S6K pathway, potentially Akt-independent pathway.