Studies have shown that deletion of the protein Grb10, which is a negative regulator of receptors for insulin and insulin-like growth factor 1, results in excessive muscle growth in mice. Lowenna J. Holt and her colleagues at the Garvan Institute of Medical Research (Sydney, Australia) investigated this phenotype more closely to determine whether it might offer new treatment avenues for diseases associated with muscle wasting. These diseases include muscular dystrophy, type 2 diabetes and some types of injury and muscle inflammation.
Holt's group examined male mice lacking Grb10 and compared their skeletal muscle physiology with that of wild-type mice. Grb10-deficient mice had greater body mass and muscle mass throughout adulthood. The larger muscles resulted from an increase in the number of myofibers (142% of wild-type) rather than an increase in fiber size. Furthermore, the weight and cross-sectional area of hindlimbs were also greater in neonatal Grb10-deficient mice than in wild-type pups (198% and 137% of wild-type, respectively). Gene set enrichment analysis showed that Grb10 deletion was associated with changes in gene expression that opposed changes typically associated with muscle wasting (FASEB J. 26, 3658–3669; 2012). “Ultimately, this might improve treatment of muscle wasting conditions,” Holt explained in a press release.
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