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Mahendra D. Mavalli, … , Marcas M. Bamman, Thomas L. Clemens
Published October 1, 2010
Citation Information: J Clin Invest. 2010;120(11):4007-4020. https://doi.org/10.1172/JCI42447.
Citation Information: J Clin Invest. 2010;120(11):4007-4020. https://doi.org/10.1172/JCI42447.
Abstract
Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not clear which effects of GH on skeletal muscle are direct and which are secondary to GH-induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal muscle development characterized by reductions in myofiber number and area as well as accompanying deficiencies in functional performance. Defective skeletal muscle development, in both GHR and IGF-1R mutants, was attributable to diminished myoblast fusion and associated with compromised nuclear factor of activated T cells import and activity. Strikingly, mice lacking GHR developed metabolic features that were not observed in the IGF-1R mutants, including marked peripheral adiposity, insulin resistance, and glucose intolerance. Insulin resistance in GHR-deficient myotubes derived from reduced IR protein abundance and increased inhibitory phosphorylation of IRS-1 on Ser 1101. These results identify distinct signaling pathways through which GHR regulates skeletal muscle development and modulates nutrient metabolism.
Authors
Mahendra D. Mavalli, Douglas J. DiGirolamo, Yong Fan, Ryan C. Riddle, Kenneth S. Campbell, Thomas van Groen, Stuart J. Frank, Mark A. Sperling, Karyn A. Esser, Marcas M. Bamman, Thomas L. Clemens
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Citation information
Citations to this article (115)
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Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society | 2011 |
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Pleiotropic effects of growth hormone signaling in aging
A Bartke |
Trends in Endocrinology and Metabolism | 2011 |
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Insulin-Like Growth Factor-1 Receptor Is Regulated by microRNA-133 during Skeletal Myogenesis
MB Huang, H Xu, SJ Xie, H Zhou, LH Qu |
PloS one | 2011 |
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