The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways
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 PtdIns-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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The PI3K/Akt/mTOR pathway is a crucial intercellular regulator of muscle hypertrophy 29.”
From Akt-dependent anabolic activity of natural and synthetic brassinosteroids in rat skeletal muscle cells (2011) · cites this paper as [29]
In the citing paper
“Akt stimulates glucose uptake, glycogen synthesis, and protein synthesis via Akt/mTOR and Akt/GSK-3β signaling networks (14) and inhibits apoptosis and protein degradation in skeletal muscle by inactivating FoxO transcription factors (15).”
From Anabolic effect of plant brassinosteroid (2011) · cites this paper as [14]
Citations
Cites
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
Self-citationRegulation of neuronal survival by the serine-threonine protein kinase Akt
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E. (1997) · Science · doi:10.1126/science.275.5300.661 · Cited by 2,436
Growth Hormone and the Insulin-Like Growth Factor System in Myogenesis*
Florini, J. R., Ewton, D. Z., & Coolican, S. A. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-5-481 · Cited by 1,148
Autonomous Control of Cell and Organ Size by CHICO, a Drosophila Homolog of Vertebrate IRS1–4
Böhni, R., Riesgo‐Escovar, J. R., Oldham, S., Brogiolo, W., Stocker, H., Andruss, B. F., Beckingham, K., & Hafen, E. (1999) · Cell · doi:10.1016/s0092-8674(00)80799-0 · Cited by 840
Drosophila S6 kinase: a regulator of cell size.
Montagne, J., Stewart, M. J., Stocker, H., Hafen, E., Kozma, S., & Thomas, G. (1999) · Science · doi:10.1126/science.285.5436.2126 · Cited by 785
Differentiation Stage-Specific Inhibition of the Raf-MEK-ERK Pathway by Akt
Rommel, C., Clarke, B. A., Zimmermann, S., Nuñez, L., Rossman, R., Reid, K., Moelling, K., Yancopoulos, G. D., & Glass, D. J. (1999) · Science · doi:10.1126/science.286.5445.1738 · Cited by 760
Self-citationMusarò, A., McCullagh, K. J. A., Naya, F. J., Olson, E. N., & Rosenthal, N. A. (1999) · Nature · doi:10.1038/23060 · Cited by 652
The Drosophila phosphoinositide 3‐kinase Dp110 promotes cell growth.
Leevers, S. J., Weinkove, D., MacDougall, L. K., Hafen, E., & Waterfield, M. D. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01049.x · Cited by 484
GOLDSPINK, G. (1999) · Journal of Anatomy · doi:10.1046/j.1469-7580.1999.19430323.x · Cited by 435
Liu, Q., Sasaki, T., Kozieradzki, I., Wakeham, A., Itie, A., Dumont, D. J., & Penninger, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.7.786 · Cited by 341
Research works printed but not linked: 3
- Engel, A. G. & Fanzine-Armstrong, C. Myology 1937 (McGraw-Hill, New York, 1994).
- Florini, J. R., Ewton, D. Z. & Coolican, S. A. Endocr. Rev. 17, 481–517 (1996).
- Yu, H. & Berkel, H. J. LA State Med. Soc. 151, 218–223 (1999).
Cited by
Sorted by citations
Items 1,001–1,004 of 1,004
Study on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12
Organotypic cultures as aging associated disease models
Sanchez, M. M., Bagdasarian, I. A., Darch, W., & Morgan, J. T. (2022) · Aging · doi:10.18632/aging.204361 · Cited by 12
Wang, H.-L., Liu, L.-L., Tan, Z.-Y., Zhou, Y., Zhang, J., Zhai, L., Xie, Q., & Liu, R.-H. (2025) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2025.104992 · Cited by 10
Lamon, S., Zacharewicz, E., Arentson-Lantz, E., Gatta, P. A. D., Ghobrial, L., Gerlinger-Romero, F., Garnham, A., Paddon-Jones, D., & Russell, A. P. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00292 · Cited by 10
Metadata
- Authors
- Rommel, C., Bodine, S. C., Clarke, B. A., Rossman, R., Nunez, L., Stitt, T. N., Yancopoulos, G. D., & Glass, D. J.
- Affiliations
- Regeneron (United States) (US)
- Corresponding author
- Glass, David J.
- Venue
- Nature Cell Biology
- Published
- 2001-10-05
- Volume
- 3
- Issue
- 11
- Pages
- 1009-1013
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W1530473805
- Cited by
- 1,583
- References
- 24
- Citations by year
- 2026: 29 · 2025: 37 · 2024: 60 · 2023: 48 · 2022: 73 · 2021: 72 · 2020: 60 · 2019: 63 · 2018: 75 · 2017: 68 · 2016: 71 · 2015: 78 · 2014: 82 · 2013: 107 · 2012: 101
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regeneron Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- insulin-like growth factor I, skeletal muscle hypertrophy, myotubes, PI3K/Akt signaling, mTOR, glycogen synthase kinase-3, calcineurin, NFAT, muscle atrophy, protein synthesis
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Carrier Proteins, Cell Differentiation, Cell Line, Insulin-Like Growth Factor I, Muscular Atrophy, Phosphoproteins, Phosphorylation, Protein Kinases, Proto-Oncogene Proteins, Signal Transduction, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Muscle, Skeletal, Cell Cycle Proteins, Calcineurin, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Eukaryotic Initiation Factors, Protein Kinase Inhibitors, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Mice, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
