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.
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The PI3K/Akt/mTOR pathway is a crucial intercellular regulator of muscle hypertrophy.
“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]
Akt stimulates glucose uptake, glycogen synthesis, and protein synthesis via Akt/mTOR and Akt/GSK-3β signaling networks and inhibits apoptosis and protein degradation in skeletal muscle by inactivating FoxO transcription factors.
“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]
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 · see citing works
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 · see citing works
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 1,092 · see citing works
Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4.
Böhni, R., Riesgo-Escovar, J., Oldham, S., Brogiolo, W., Stocker, H., Andruss, B., Beckingham, K., & Hafen, E. (1999) · Cell · doi:10.1016/s0092-8674(00)80799-0 · Cited by 863 · see citing works
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 · see citing works
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 759 · see citing works
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 · see citing works
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 487 · see citing works
GOLDSPINK, G. (1999) · Journal of Anatomy · doi:10.1046/j.1469-7580.1999.19430323.x · Cited by 435 · see citing works
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 · see citing works
PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development
Huang, H., Potter, C. J., Tao, W., Li, D., Brogiolo, W., Hafen, E., Sun, H., & Xu, T. (1999) · Development · doi:10.1242/dev.126.23.5365 · Cited by 321 · see citing works
Svegliati-Baroni, G., Ridolfi, F., Di Sario, A., Casini, A., Marucci, L., Gaggiotti, G., Orlandoni, P., Macarri, G., Perego, L., Benedetti, A., et al. (1999) · Hepatology · doi:10.1002/hep.510290632 · Cited by 320 · see citing works
Calcineurin Signaling and Muscle Remodeling
Olson, E. N., & Williams, R. S. (2000) · Cell · doi:10.1016/s0092-8674(00)80880-6 · Cited by 291 · see citing works
Adams, G. R., & Haddad, F. (1996) · Journal of Applied Physiology · doi:10.1152/jappl.1996.81.6.2509 · Cited by 287 · see citing works
Calcineurin Activity Is Required for the Initiation of Skeletal Muscle Differentiation
Friday, B. B., Horsley, V., & Pavlath, G. K. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.3.657 · Cited by 242 · see citing works
The Inositol Phosphatase SHIP Inhibits Akt/PKB Activation in B Cells
Aman, M. J., Lamkin, T. D., Okada, H., Kurosaki, T., & Ravichandran, K. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.33922 · Cited by 217 · see citing works
Eves, E. M., Xiong, W., Bellacosa, A., Kennedy, S. G., Tsichlis, P. N., Rosner, M. R., & Hay, N. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.4.2143 · Cited by 186 · see citing works
Azpiazu, I., Saltiel, A. R., DePaoli-Roach, A. A., & Lawrence, J. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.9.5033 · Cited by 152 · see citing works
SEMSARIAN, C., SUTRAVE, P., RICHMOND, D. R., & GRAHAM, R. M. (1999) · Biochemical Journal · doi:10.1042/bj3390443 · Cited by 106 · see citing works
Wesselborg, S., Fruman, D. A., Sagoo, J. K., Bierer, B. E., & Burakoff, S. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1274 · Cited by 105 · see citing works
SHIP inhibits Akt activation in B cells through regulation of Akt membrane localization
Carver, D. J., Aman, M. J., & Ravichandran, K. S. (2000) · Blood · doi:10.1182/blood.v96.4.1449 · Cited by 59 · see citing works
FcγRIIb Modulation of Surface Immunoglobulin-induced Akt Activation in Murine B Cells
Jacob, A., Cooney, D. S., Tridandapani, S., Kelley, T. W., & Coggeshall, K. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.19.13704 · Cited by 58 · see citing works
Renganathan, M., Messi, M. L., Schwartz, R. J., & Delbono, O. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01225-8 · Cited by 42 · see citing works
Cloning and Analysis of Neurotrophic Factor Receptors Using Function-based StrategiesPreprint
Glass, D. J., Gies, D. R., Stitt, T. N., et al. (1992) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1992.057.01.007 · Cited by 2 · see citing works
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mTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555 · see citing works
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521 · see citing works
Self-citationSandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012 · see citing works
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 · see citing works
Self-citationStitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964 · see citing works
Self-citationMultiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539 · see citing works
Mechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492 · see citing works
Cellular and molecular mechanisms of muscle atrophy
Bonaldo, P., & Sandri, M. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.010389 · Cited by 1,284 · see citing works
Skeletal muscle hypertrophy and atrophy signaling pathways
Glass, D. J. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.04.018 · Cited by 1,106 · see citing works
Self-citationThe Molecular Basis of Skeletal Muscle Atrophy
Jackman, R. W., & Kandarian, S. C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00579.2003 · Cited by 1,008 · see citing works
Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration
Heredia, J. E., Mukundan, L., Chen, F. M., Mueller, A. A., Deo, R. C., Locksley, R. M., Rando, T. A., & Chawla, A. (2013) · Cell · doi:10.1016/j.cell.2013.02.053 · Cited by 818 · see citing works
Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models
Schiaffino, S., & Mammucari, C. (2011) · Skeletal Muscle · doi:10.1186/2044-5040-1-4 · Cited by 816 · see citing works
Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size
Trendelenburg, A. U., Meyer, A., Rohner, D., Boyle, J., Hatakeyama, S., & Glass, D. J. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00105.2009 · Cited by 792 · see citing works
The Molecular Bases of Training Adaptation
Coffey, V. G., & Hawley, J. A. (2007) · Sports Medicine · doi:10.2165/00007256-200737090-00001 · Cited by 756 · see citing works
Satellite Cells and Skeletal Muscle Regeneration
Dumont, N. A., Bentzinger, C. F., Sincennes, M., & Rudnicki, M. A. (2015) · Comprehensive Physiology · doi:10.1002/cphy.c140068 · Cited by 719 · see citing works
Glucocorticoid-Induced Skeletal Muscle Atrophy
Schakman, O., Kalista, S., Barbé, C., Loumaye, A., & Thissen, J. P. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.05.036 · Cited by 705 · see citing works
Signalling pathways that mediate skeletal muscle hypertrophy and atrophy
Glass, D. J. (2003) · Nature Cell Biology · doi:10.1038/ncb0203-87 · Cited by 694 · see citing works
Self-citationBentzinger, C. F., Romanino, K., Cloëtta, D., Lin, S., Mascarenhas, J. B., Oliveri, F., Xia, J., Casanova, E., Costa, C. F., Brink, M., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.10.002 · Cited by 640 · see citing works
Oxidative Stress, Molecular Inflammation and Sarcopenia
Meng, S.-J., & Yu, L.-J. (2010) · International Journal of Molecular Sciences · doi:10.3390/ijms11041509 · Cited by 637 · see citing works
Sacheck, J. M., Ohtsuka, A., McLary, S. C., & Goldberg, A. L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00073.2004 · Cited by 606 · see citing works
A review on the mechanisms of blood-flow restriction resistance training-induced muscle hypertrophy
Pearson, S. J., & Hussain, S. R. (2015) · Sports Medicine · doi:10.1007/s40279-014-0264-9 · Cited by 592 · see citing works
Signaling pathways controlling skeletal muscle mass
Egerman, M. A., & Glass, D. J. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.857291 · Cited by 555 · see citing works
Self-citationMechanisms of glucocorticoid-induced myopathy
Schakman, O., Gilson, H., & Thissen, J. P. (2008) · Journal of Endocrinology · doi:10.1677/joe-07-0606 · Cited by 521 · see citing works
Atherton, P. J., Babraj, J. A., Smith, K., Singh, J., Rennie, M. J., & Wackerhage, H. (2005) · The FASEB Journal · doi:10.1096/fj.04-2179fje · Cited by 475 · see citing works
Insulin signaling in health and disease
Saltiel, A. R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142241 · Cited by 446 · see citing works
Conditional Activation of Akt in Adult Skeletal Muscle Induces Rapid Hypertrophy
Lai, K.-M. V., Gonzalez, M., Poueymirou, W. T., Kline, W. O., Na, E., Zlotchenko, E., Stitt, T. N., Economides, A. N., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9295-9304.2004 · Cited by 442 · see citing works
Self-citationCellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness
Ryall, J. G., Schertzer, J. D., & Lynch, G. S. (2008) · Biogerontology · doi:10.1007/s10522-008-9131-0 · Cited by 423 · see citing works
Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease
Lynch, G. S., & Ryall, J. G. (2008) · Physiological Reviews · doi:10.1152/physrev.00028.2007 · Cited by 410 · see citing works
Pallafacchina, G., Calabria, E., Serrano, A. L., Kalhovde, J. M., & Schiaffino, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142166599 · Cited by 402 · see citing works
Muscle protein synthesis in response to nutrition and exercise
Atherton, P. J., & Smith, K. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.225003 · Cited by 401 · see citing works
Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese Mice
Izumiya, Y., Hopkins, T., Morris, C., Sato, K., Zeng, L., Viereck, J., Hamilton, J. A., Ouchi, N., LeBrasseur, N. K., & Walsh, K. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.003 · Cited by 395 · see citing works
Control of the size of the human muscle mass
Rennie, M. J., Wackerhage, H., Spangenburg, E. E., & Booth, F. W. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.052102.134444 · Cited by 399 · see citing works
Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways
Rodriguez, J., Vernus, B., Chelh, I., Cassar-Malek, I., Gabillard, J. C., Hadj Sassi, A., Seiliez, I., Picard, B., & Bonnieu, A. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1689-x · Cited by 397 · see citing works
Sarcopenia, frailty and their prevention by exercise
Nascimento, C. M., Ingles, M., Salvador-Pascual, A., Cominetti, M. R., Gomez-Cabrera, M. C., & Viña, J. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.035 · Cited by 396 · see citing works
Ohanna, M., Sobering, A. K., Lapointe, T., Lorenzo, L., Praud, C., Petroulakis, E., Sonenberg, N., Kelly, P. A., Sotiropoulos, A., & Pende, M. (2005) · Nature Cell Biology · doi:10.1038/ncb1231 · Cited by 392 · see citing works
Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy
Risson, V., Mazelin, L., Roceri, M., Sanchez, H., Moncollin, V., Corneloup, C., Richard-Bulteau, H., Vignaud, A., Baas, D., Defour, A., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200903131 · Cited by 381 · see citing works
Aging, exercise, and muscle protein metabolism
Koopman, R., & van Loon, L. J. C. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91551.2008 · Cited by 371 · see citing works
Signaling pathways perturbing muscle mass.
Glass, D. J. (2010) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e32833862df · Cited by 359 · see citing works
Self-citationRamos, F. J., Chen, S. C., Garelick, M. G., Dai, D.-F., Liao, C.-Y., Schreiber, K. H., MacKay, V. L., An, E. H., Strong, R., Ladiges, W. C., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003802 · Cited by 349 · see citing works
Patterns of gene expression in atrophying skeletal muscles: response to food deprivation
Jagoe, R. T., Lecker, S. H., Gomes, M., & Goldberg, A. L. (2002) · The FASEB Journal · doi:10.1096/fj.02-0312com · Cited by 344 · see citing works
Sandri, M., Barberi, L., Bijlsma, A. Y., Blaauw, B., Dyar, K. A., Milan, G., Mammucari, C., Meskers, C. G. M., Pallafacchina, G., Paoli, A., et al. (2013) · Biogerontology · doi:10.1007/s10522-013-9432-9 · Cited by 340 · see citing works
Early signaling responses to divergent exercise stimuli in skeletal muscle from well-trained humans
Coffey, V. G., Zhong, Z., Shield, A., Canny, B. J., Chibalin, A. V., Zierath, J. R., & Hawley, J. A. (2006) · The FASEB Journal · doi:10.1096/fj.05-4809fje · Cited by 336 · see citing works
Reza, M. M., Subramaniyam, N., Sim, C. M., Ge, X., Sathiakumar, D., McFarlane, C., Sharma, M., & Kambadur, R. (2017) · Nature Communications · doi:10.1038/s41467-017-01131-0 · Cited by 335 · see citing works
Perrini, S., Laviola, L., Carreira, M. C., Cignarelli, A., Natalicchio, A., & Giorgino, F. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0431 · Cited by 317 · see citing works
Lach-Trifilieff, E., Minetti, G. C., Sheppard, K., Ibebunjo, C., Feige, J. N., Hartmann, S., Brachat, S., Rivet, H., Koelbing, C., Morvan, F., et al. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01307-13 · Cited by 306 · see citing works
Self-citationThe role of skeletal muscle mTOR in the regulation of mechanical load‐induced growth
Goodman, C. A., Frey, J. W., Mabrey, D. M., Jacobs, B. L., Lincoln, H. C., You, J., & Hornberger, T. A. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.218255 · Cited by 297 · see citing works
Effects of Resistance Exercise on Bone Health
Hong, A. R., & Kim, S. W. (2018) · Endocrinology and Metabolism · doi:10.3803/enm.2018.33.4.435 · Cited by 291 · see citing works
MicroRNAs in skeletal muscle: Their role and regulation in development, disease and function
Güller, I., & Russell, A. P. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.194175 · Cited by 290 · see citing works
Exercise and gene expression: physiological regulation of the human genome through physical activity
Booth, F. W., Chakravarthy, M. V., & Spangenburg, E. E. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.019265 · Cited by 277 · see citing works
Disuse of the musculo-skeletal system in space and on earth
Narici, M. V., & de Boer, M. D. (2011) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1556-x · Cited by 270 · see citing works
Lipid modulation of skeletal muscle mass and function
Lipina, C., & Hundal, H. S. (2017) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12144 · Cited by 247 · see citing works
The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass
Winbanks, C. E., Chen, J. L., Qian, H., Liu, Y., Bernardo, B. C., Beyer, C., Watt, K. I., Thomson, R. E., Connor, T., Turner, B. J., et al. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201211134 · Cited by 225 · see citing works
Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting
Zanders, L., Kny, M., Hahn, A., Schmidt, S., Wundersitz, S., Todiras, M., Lahmann, I., Bandyopadhyay, A., Wollersheim, T., Kaderali, L., et al. (2022) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12867 · Cited by 225 · see citing works
Osteocalcin is necessary and sufficient to maintain muscle mass in older mice
Mera, P., Laue, K., Wei, J., Berger, J. M., & Karsenty, G. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.07.002 · Cited by 223 · see citing works
Winbanks, C. E., Weeks, K. L., Thomson, R. E., Sepulveda, P. V., Beyer, C., Qian, H., Chen, J. L., Allen, J. M., Lancaster, G. I., Febbraio, M. A., et al. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201109091 · Cited by 218 · see citing works
Roberts, M. D., McCarthy, J. J., Hornberger, T. A., Phillips, S. M., Mackey, A. L., Nader, G. A., Boppart, M. D., Kavazis, A. N., Reidy, P. T., Ogasawara, R., et al. (2023) · Physiological Reviews · doi:10.1152/physrev.00039.2022 · Cited by 214 · see citing works
Mayhew, D. L., Kim, J.-S., Cross, J. M., Ferrando, A. A., & Bamman, M. M. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91234.2008 · Cited by 215 · see citing works
Treatment of sporadic inclusion body myositis with bimagrumab
Amato, A. A., Sivakumar, K., Goyal, N., David, W. S., Salajegheh, M., Praestgaard, J., Lach-Trifilieff, E., Trendelenburg, A.-U., Laurent, D., Glass, D. J., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000001070 · Cited by 210 · see citing works
Self-citationImplications of Insulin-Like Growth Factor-1 in Skeletal Muscle and Various Diseases
Ahmad, S. S., Ahmad, K., Lee, E. J., Lee, Y.-H., & Choi, I. (2020) · Cells · doi:10.3390/cells9081773 · Cited by 202 · see citing works
Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass
Frost, R. A., & Lang, C. H. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00089.2007 · Cited by 200 · see citing works
Molecular Networks of Human Muscle Adaptation to Exercise and Age
Phillips, B. E., Williams, J. P., Gustafsson, T., Bouchard, C., Rankinen, T., Knudsen, S., Smith, K., Timmons, J. A., & Atherton, P. J. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003389 · Cited by 199 · see citing works
Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle
Edstrom, E., Altun, M., Hagglund, M., & Ulfhake, B. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.7.663 · Cited by 196 · see citing works
Amelioration of muscle wasting by glucagon‐like peptide‐1 receptor agonist in muscle atrophy
Hong, Y., Lee, J. H., Jeong, K. W., Choi, C. S., & Jun, H. (2019) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12434 · Cited by 188 · see citing works
Differential role of insulin/IGF-1 receptor signaling in muscle growth and glucose homeostasis
O’Neill, B. T., Lauritzen, H. P. M. M., Hirshman, M. F., Smyth, G., Goodyear, L. J., & Kahn, C. R. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.037 · Cited by 171 · see citing works
mTOR pathway as a target in tissue hypertrophy
Lee, C.-H., Inoki, K., & Guan, K.-L. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105359 · Cited by 179 · see citing works
Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle
Wang, X., Blagden, C., Fan, J., Nowak, S. J., Taniuchi, I., Littman, D. R., & Burden, S. J. (2005) · Genes & Development · doi:10.1101/gad.1318305 · Cited by 177 · see citing works
Inflammation and age-associated skeletal muscle deterioration (sarcopaenia)
Wang, J., Leung, K.-S., Chow, S. K.-H., & Cheung, W.-H. (2017) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2017.05.006 · Cited by 173 · see citing works
mTOR Signaling and the Molecular Adaptation to Resistance Exercise
BODINE, S. C. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000233797.24035.35 · Cited by 171 · see citing works
Self-citationMechanotransduction and the regulation of mTORC1 signaling in skeletal muscle
Hornberger, T. A. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.05.007 · Cited by 170 · see citing works
mTOR function in skeletal muscle hypertrophy: Increased ribosomal RNA via cell cycle regulators
Nader, G. A., McLoughlin, T. J., & Esser, K. A. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00165.2005 · Cited by 166 · see citing works
Cannavino, J., Brocca, L., Sandri, M., Grassi, B., Bottinelli, R., & Pellegrino, M. A. (2015) · The Journal of Physiology · doi:10.1113/jphysiol.2014.286740 · Cited by 166 · see citing works
JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy
Raffaello, A., Milan, G., Masiero, E., Carnio, S., Lee, D., Lanfranchi, G., Goldberg, A. L., & Sandri, M. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201001136 · Cited by 156 · see citing works
Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy
Bentzinger, C. F., Lin, S., Romanino, K., Castets, P., Guridi, M., Summermatter, S., Handschin, C., Tintignac, L. A., Hall, M. N., & Rüegg, M. A. (2013) · Skeletal Muscle · doi:10.1186/2044-5040-3-6 · Cited by 153 · see citing works
Signaling pathways weigh in on decisions to make or break skeletal muscle
Guttridge, D. C. (2004) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/01.mco.0000134364.61406.26 · Cited by 149 · see citing works
Dyle, M. C., Ebert, S. M., Cook, D. P., Kunkel, S. D., Fox, D. K., Bongers, K. S., Bullard, S. A., Dierdorff, J. M., & Adams, C. M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.556241 · Cited by 138 · see citing works
ERK2 is required for efficient terminal differentiation of skeletal myoblasts
Li, J., & Johnson, S. E. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.05.051 · Cited by 137 · see citing works
Muscle Wasting and Changes in Muscle Protein Metabolism in Chronic Obstructive Pulmonary Disease
Jagoe, R. T., & Engelen, M. P. K. J. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00004608 · Cited by 134 · see citing works
Important role for AMPKαl in limiting skeletal muscle cell hypertrophy
Mounier, R., Lantier, L., Leclerc, J., Sotiropoulos, A., Pende, M., Daegelen, D., Sakamoto, K., Foretz, M., & Viollet, B. (2009) · The FASEB Journal · doi:10.1096/fj.08-119057 · Cited by 133 · see citing works
Philp, A., Hamilton, D. L., & Baar, K. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00941.2010 · Cited by 131 · see citing works
Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H
Kudryashova, E., Kramerova, I., & Spencer, M. J. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59581 · Cited by 119 · see citing works
Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle
Coffey, V. G., Pilegaard, H., Garnham, A. P., O'Brien, B. J., & Hawley, J. A. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91221.2008 · Cited by 116 · see citing works
Wang, H.-V., Chang, L.-W., Brixius, K., Wickström, S. A., Montanez, E., Thievessen, I., Schwander, M., Müller, U., Bloch, W., Mayer, U., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200707175 · Cited by 112 · see citing works
Autophagy as a Potential Target for Sarcopenia: AUTOPHAGY REGULATION IN SARCOPENIA
Fan, J., Kou, X., Jia, S., Yang, X., Yang, Y., & Chen, N. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25260 · Cited by 101 · see citing works
Roberts, M. D., Haun, C. T., Mobley, C. B., Mumford, P. W., Romero, M. A., Roberson, P. A., Vann, C. G., & McCarthy, J. J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00834 · Cited by 107 · see citing works
Sex hormones and skeletal muscle weakness
Sipilä, S., Narici, M., Kjaer, M., Pöllänen, E., Atkinson, R. A., Hansen, M., & Kovanen, V. (2013) · Biogerontology · doi:10.1007/s10522-013-9425-8 · Cited by 106 · see citing works
A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice
Hunt, L. C., Stover, J., Haugen, B., Shaw, T. I., Li, Y., Pagala, V. R., Finkelstein, D., Barton, E. R., Fan, Y., Labelle, M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.094 · Cited by 90 · see citing works
Mieulet, V., Roceri, M., Espeillac, C., Sotiropoulos, A., Ohanna, M., Oorschot, V., Klumperman, J., Sandri, M., & Pende, M. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00499.2006 · Cited by 99 · see citing works
Ono, T., Takada, S., Kinugawa, S., & Tsutsui, H. (2015) · Experimental Physiology · doi:10.1113/ep085049 · Cited by 99 · see citing works
Testosterone improves the regeneration of old and young mouse skeletal muscle
Serra, C., Tangherlini, F., Rudy, S., Lee, D., Toraldo, G., Sandor, N. L., Zhang, A., Jasuja, R., & Bhasin, S. (2013) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gls083 · Cited by 87 · see citing works
Aguilar‐Agon, K. W., Capel, A. J., Martin, N. R. W., Player, D. J., & Lewis, M. P. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28923 · Cited by 84 · see citing works
Cisternas, F., Morales, M. G., Meneses, C., Simon, F., Brandan, E., Abrigo, J., Vazquez, Y., & Cabello-Verrugio, C. (2015) · Clinical Science · doi:10.1042/cs20140215 · Cited by 83 · see citing works
Prevention of Disuse Muscle Atrophy by Dietary Ingestion of 8-Prenylnaringenin in Denervated Mice
Mukai, R., Horikawa, H., Fujikura, Y., Kawamura, T., Nemoto, H., Nikawa, T., & Terao, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045048 · Cited by 83 · see citing works
Kazior, Z., Willis, S. J., Moberg, M., Apró, W., Calbet, J. A. L., Holmberg, H.-C., & Blomstrand, E. (2016) · PLOS ONE · doi:10.1371/journal.pone.0149082 · Cited by 82 · see citing works
Jaiswal, N., Gavin, M., Loro, E., Sostre‐Colón, J., Roberson, P. A., Uehara, K., Rivera‐Fuentes, N., Neinast, M., Arany, Z., Kimball, S. R., et al. (2022) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12846 · Cited by 79 · see citing works
Skeletal Muscle Atrophy: Discovery of Mechanisms and Potential Therapies
Ebert, S. M., Al-Zougbi, A., Bodine, S. C., & Adams, C. M. (2019) · Physiology · doi:10.1152/physiol.00003.2019 · Cited by 80 · see citing works
Vignaud, J., Loiseau, C., Hérault, J., Mayer, C., Côme, M., Martin, I., & Ulmann, L. (2023) · Antioxidants · doi:10.3390/antiox12051050 · Cited by 72 · see citing works
Hamilton, D. L., Philp, A., MacKenzie, M. G., & Baar, K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011624 · Cited by 71 · see citing works
von Walden, F., Liu, C., Aurigemma, N., & Nader, G. A. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00144.2016 · Cited by 70 · see citing works
Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition
Goncalves, M. D., Pistilli, E. E., Balduzzi, A., Birnbaum, M. J., Lachey, J., Khurana, T. S., & Ahima, R. S. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012707 · Cited by 69 · see citing works
Acute myotube protein synthesis regulation by IL-6-related cytokines
Gao, S., Durstine, J. L., Koh, H.-J., Carver, W. E., Frizzell, N., & Carson, J. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00112.2017 · Cited by 69 · see citing works
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
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