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

Christian Rommel, Sue C. Bodine, Brian A. Clarke, Roni Rossman, Lorna Nunez, Trevor N. Stitt, George D. Yancopoulos, David J. Glass

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish (US)
Pages (from-to)1009-1013
Number of pages5
JournalNature Cell Biology
Volume3
Issue number11
DOIs
StatePublished - 2001
Externally publishedYes

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Glycogen Synthase Kinase 3
Skeletal Muscle Fibers
Somatomedins
Sirolimus
Hypertrophy
Calcineurin
Atrophy
Skeletal Muscle
NFATC Transcription Factors
Muscular Atrophy
Myoblasts
Phosphatidylinositol 3-Kinases
Muscles
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rommel, C., Bodine, S. C., Clarke, B. A., Rossman, R., Nunez, L., Stitt, T. N., ... Glass, D. J. (2001). Mediation of IGF-1-induced skeletal myotube hypertrophy by Pl(3)K/Alt/mTOR and Pl(3)K/Akt/GSK3 pathways. Nature Cell Biology, 3(11), 1009-1013. https://doi.org/10.1038/ncb1101-1009

Mediation of IGF-1-induced skeletal myotube hypertrophy by Pl(3)K/Alt/mTOR and Pl(3)K/Akt/GSK3 pathways. / Rommel, Christian; Bodine, Sue C.; Clarke, Brian A.; Rossman, Roni; Nunez, Lorna; Stitt, Trevor N.; Yancopoulos, George D.; Glass, David J.

In: Nature Cell Biology, Vol. 3, No. 11, 2001, p. 1009-1013.

Research output: Contribution to journalArticle

Rommel, C, Bodine, SC, Clarke, BA, Rossman, R, Nunez, L, Stitt, TN, Yancopoulos, GD & Glass, DJ 2001, 'Mediation of IGF-1-induced skeletal myotube hypertrophy by Pl(3)K/Alt/mTOR and Pl(3)K/Akt/GSK3 pathways', Nature Cell Biology, vol. 3, no. 11, pp. 1009-1013. https://doi.org/10.1038/ncb1101-1009
Rommel, Christian ; Bodine, Sue C. ; Clarke, Brian A. ; Rossman, Roni ; Nunez, Lorna ; Stitt, Trevor N. ; Yancopoulos, George D. ; Glass, David J. / Mediation of IGF-1-induced skeletal myotube hypertrophy by Pl(3)K/Alt/mTOR and Pl(3)K/Akt/GSK3 pathways. In: Nature Cell Biology. 2001 ; Vol. 3, No. 11. pp. 1009-1013.
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