{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:05:54Z","timestamp":1791216354129,"version":"4.1.0"},"reference-count":46,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We reported previously that IGF-I inhibits burn-induced muscle proteolysis. Recent studies suggest that activation of the phosphotidylinositol 3-kinase (PI3K)\/Akt signaling pathway with downstream phosphorylation of Forkhead box O transcription factors is an important mechanism of IGF-I-induced anabolic effects in skeletal muscle. The potential roles of other mechanisms in the anabolic effects of IGF-I are less well understood. In this study we tested the roles of mammalian target of rapamycin and glycogen synthase kinase-3\u03b2 (GSK-3\u03b2) phosphorylation as well as MAPK- and calcineurin-dependent signaling pathways in the anticatabolic effects of IGF-I by incubating extensor digitorum longus muscles from burned rats in the presence of IGF-I and specific signaling pathway inhibitors. Surprisingly, the PI3K inhibitors LY294002 and wortmannin reduced basal protein breakdown. No additional inhibition by IGF-I was noticed in the presence of LY294002 or wortmannin. Inhibition of proteolysis by IGF-I was associated with phosphorylation (inactivation) of GSK-3\u03b2. In addition, the GSK-3\u03b2 inhibitors, lithium chloride and thiadiazolidinone-8, reduced protein breakdown in a similar fashion as IGF-I. Lithium chloride, but not thiadiazolidinone-8, increased the levels of phosphorylated Foxo 1 in incubated muscles from burned rats. Inhibitors of mammalian target of rapamycin, MAPK, and calcineurin did not prevent the IGF-I-induced inhibition of muscle proteolysis. Our results suggest that IGF-I inhibits protein breakdown at least in part through a PI3K\/Akt\/GSK3\u03b2-dependent mechanism. Additional experiments showed that similar mechanisms were responsible for the effect of IGF-I in muscle from nonburned rats. Taken together with recent reports in the literature, the present results suggest that IGF-I inhibits protein breakdown in skeletal muscle by multiple mechanisms, including PI3K\/Akt-mediated inactivation of GSK-3\u03b2 and Foxo transcription factors.<\/jats:p>","DOI":"10.1210\/en.2004-0869","type":"journal-article","created":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T01:34:21Z","timestamp":1112319261000},"page":"3141-3149","source":"Crossref","is-referenced-by-count":47,"title":["Protein Breakdown in Muscle from Burned Rats Is Blocked by Insulin-Like Growth Factor I and Glycogen Synthase Kinase-3\u03b2 Inhibitors"],"prefix":"10.1210","volume":"146","author":[{"given":"Cheng-Hui","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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