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1 Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, PA, USA; Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: erbarton{at}biochem.dental.upenn.edu.
Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein, but does produce different E peptide extensions which have been reported to modify the potency of IGF-I. Viral mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2 week old and 6 month old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV treated muscles than control muscles at 1, 2 and 4 months post-injection. Viral injection of IGF-IB produced 2-7 fold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 months post-injection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6 month old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.
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