Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats

Muscle hypertrophy is the product of increased drive through protein synthetic pathways and the incorporation of newly divided satellite cells. Gains in muscle mass and strength can be achieved through exercise regimens that include resistance training. Increased insulin-like growth factor-I (IGF-I) can also promote hypertrophy through increased protein synthesis and satellite cell proliferation. However, it is not known whether the combined effect of IGF-I and resistance training results in an additive hypertrophic response. Therefore, rats in which viral administration of IGF-I was directed to one limb were subjected to ladder climbing to test the interaction of each intervention on muscle mass and strength. After 8 wk of resistance training, a 23.3% increase in muscle mass and a 14.4% increase in peak tetanic tension (Po) were observed in the flexor hallucis longus (FHL). Viral expression of IGF-I without resistance training produced a 14.8% increase in mass and a 16.6% increase in Po in the FHL. The combined interventions produced a 31.8% increase in muscle mass and a 28.3% increase in Po in the FHL. Therefore, the combination of resistance training and overexpression of IGF-I induced greater hypertrophy than either treatment alone. The effect of increased IGF-I expression on the loss of muscle mass associated with detraining was also addressed. FHL muscles treated with IGF-I lost only 4.8% after detraining, whereas the untreated FHL lost 8.3% muscle mass. These results suggest that a combination of resistance training and overexpression of IGF-I could be an effective measure for attenuating the loss of training-induced adaptations.

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Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01405.2005 ◽

2006 ◽

Vol 100 (6) ◽

pp. 1778-1784 ◽

Cited By ~ 81

Author(s):

Elisabeth R. Barton

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Muscle Mass ◽

Muscle Hypertrophy ◽

Muscle Development ◽

Muscle Size ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I

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-wk-old and 6-mo-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 mo postinjection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, 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-mo-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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Viral expression of insulin-like growth factor I E-peptides increases skeletal muscle mass but at the expense of strength

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00008.2014 ◽

2014 ◽

Vol 306 (8) ◽

pp. E965-E974 ◽

Cited By ~ 12

Author(s):

Becky K. Brisson ◽

Janelle Spinazzola ◽

SooHyun Park ◽

Elisabeth R. Barton

Keyword(s):

Skeletal Muscle ◽

Cell Proliferation ◽

Growth Factor ◽

Muscle Mass ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I

Insulin-like growth factor I (IGF-I) is a protein that regulates and promotes growth in skeletal muscle. The IGF-I precursor polypeptide contains a COOH-terminal extension called the E-peptide. Alternative splicing in the rodent produces two isoforms, IA and IB, where the mature IGF-I in both isoforms is identical yet the E-peptides, EA and EB, share less than 50% homology. Recent in vitro studies show that the E-peptides can enhance IGF-I signaling, leading to increased myoblast cell proliferation and migration. To determine the significance of these actions in vivo and to evaluate if they are physiologically beneficial, EA and EB were expressed in murine skeletal muscle via viral vectors. The viral constructs ensured production of E-peptides without the influence of additional IGF-I through an inactivating mutation in mature IGF-I. E-peptide expression altered ERK1/2 and Akt phosphorylation and increased satellite cell proliferation. EB expression resulted in significant muscle hypertrophy that was IGF-I receptor dependent. However, the increased mass was associated with a loss of muscle strength. EA and EB have similar effects in skeletal muscle signaling and on satellite cells, but EB is more potent at increasing muscle mass. Although sustained EB expression may drive hypertrophy, there are significant physiological consequences for muscle.

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