Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways

摘要: Skeletal muscle is composed of multinucleated fibres, formed after the differentiation and fusion myoblast precursors. atrophy hypertrophy refer to changes in diameter these pre-existing fibres. The prevention would provide an obvious clinical benefit; insulin-like growth factor 1 (IGF-1) a promising anti-atrophy agent because its ability promote hypertrophy. However, signalling pathways by which IGF-1 promotes remain unclear, with roles suggested for both calcineurin/NFAT (nuclear activated T cells) pathway PtdIns-3-OH kinase (PI(3)K)/Akt pathway. Here we employ battery approaches examine during hypertrophic response cultured myotubes IGF-1. We report that Akt activating downstream previously implicated protein synthesis: mammalian target rapamycin (mTOR) phosphorylating thereby inhibiting glycogen synthase 3 (GSK3). In contrast, addition demonstrating calcineurin does not mediate IGF-1-induced hypertrophy, show unexpectedly acts via antagonize myotube