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Figure 5 Signaling Pathways of Disuse and Inflammation
Reduced insulin growth factor-1 (IGF-1) tissue level and insulin resistance combine to decrease phosphorylation of phospatidyinositol-2-OH kinase (PI3K), which in turn reduces activation of Akt (protein kinase B), thereby reducing protein synthesis via reduced phosphorylation of mammalian target of rapamycin (mTOR) and glucogen synthase kinase (GSK). Reduced Akt activation increases activity of forkhead box O (FOXO) transcription factors, thereby activating the ubiquitin-proteasome pathway and promoting protein degradation. Reduced IGF-1 levels and insulin resistance activate caspase-3, resulting in protein breakdown and degradation. Whether activated caspase-3 results in muscle apoptosis is controversial.
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