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IGF-1 increases skeletal muscle protein synthesis via PI3K\/Akt\/mTOR and PI3K\/Akt\/GSK3\u03b2 pathways. PI3K\/Akt can also inhibit FoxOs and suppress transcription of E3 ubiquitin ligases that regulate ubiquitin proteasome system (UPS)-mediated protein degradation. Autophagy is likely inhibited by IGF-1 via mTOR and FoxO signaling, although the contribution of autophagy regulation in IGF-1-mediated inhibition of skeletal muscle atrophy remains to be determined. Evidence has suggested that IGF-1\/Akt can inhibit muscle atrophy-inducing cytokine and myostatin signaling via inhibition of the NF-\u03ba\u0392 and Smad pathways, respectively. Several miRNAs have been found to regulate IGF-1 signaling in skeletal muscle, and these miRs are likely regulated in different pathological conditions and contribute to the development of muscle atrophy. IGF-1 also potentiates skeletal muscle regeneration via activation of skeletal muscle stem (satellite) cells, which may contribute to muscle hypertrophy and\/or inhibit atrophy. Importantly, IGF-1 levels and IGF-1R downstream signaling are suppressed in many chronic disease conditions and likely result in muscle atrophy via the combined effects of altered protein synthesis, UPS activity, autophagy, and muscle regeneration.<\/jats:p>","DOI":"10.3390\/cells9091970","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T09:05:37Z","timestamp":1598432737000},"page":"1970","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":694,"title":["Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-1497","authenticated-orcid":false,"given":"Tadashi","family":"Yoshida","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute, John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-48, New Orleans, LA 70112, USA"},{"name":"Department of Physiology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Delafontaine","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute, John W. Deming Department of Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-48, New Orleans, LA 70112, USA"},{"name":"Department of Physiology, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1590\/1980-57642018dn12-020003","article-title":"Physical exercise, IGF-1 and cognition A systematic review of experimental studies in the elderly","volume":"12","author":"Stein","year":"2018","journal-title":"Dement. Neuropsychol."},{"key":"ref_2","first-page":"105","article-title":"Effect of physical activity on IGF-1 and IGFBP levels in the context of civilization diseases prevention","volume":"67","author":"Majorczyk","year":"2016","journal-title":"Rocz. Panstw. Zakl. 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