Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Gehrig, S. M., Ryall, J. G., Schertzer, J. D., & Lynch, G. S. Experimental Physiology, 93(11):1190–1198, November, 2008. doi abstract bibtex Contraction-mediated injury is a major contributing factor to the pathophysiology of muscular dystrophy and therefore therapies that can attenuate this type of injury have clinical relevance. Systemic administration of insulin-like growth factor-I (IGF-I) has been shown to improve muscle function in dystrophic mdx mice, an effect associated with a shift towards a more oxidative muscle phenotype and a reduced susceptibility to contraction-mediated damage. The actions of IGF-I in vivo are modulated by IGF binding proteins (IGFBPs), which generally act to inhibit IGF-I signalling. We tested the hypothesis that an analogue of IGF-I (LR IGF-I), which has significantly reduced binding affinity for IGFBPs, would improve the dystrophic pathology by reducing the susceptibility to muscle injury. Dystrophic mdx and wild-type (C57BL/10) mice were administered LR IGF-I continuously ( approximately 1.5 mg kg(-1) day(-1)) via osmotic mini-pump for 4 weeks. Administration of LR IGF-I reduced the susceptibility of extensor digitorum longus, soleus and diaphragm muscles to contraction damage, as evident from lower force deficits after a protocol of lengthening contractions. In contrast to the mechanism of protection conferred by administration of IGF-I, the protection conferred by LR IGF-I was independent of changes in muscle fatigue and oxidative metabolism. This study further indicates that modulation of IGF-I signalling has therapeutic potential for muscular diseases.
@article{gehrig_insulin-like_2008,
title = {Insulin-like growth factor-{I} analogue protects muscles of dystrophic mdx mice from contraction-mediated damage},
volume = {93},
issn = {0958-0670},
doi = {10.1113/expphysiol.2008.042838},
abstract = {Contraction-mediated injury is a major contributing factor to the pathophysiology of muscular dystrophy and therefore therapies that can attenuate this type of injury have clinical relevance. Systemic administration of insulin-like growth factor-I (IGF-I) has been shown to improve muscle function in dystrophic mdx mice, an effect associated with a shift towards a more oxidative muscle phenotype and a reduced susceptibility to contraction-mediated damage. The actions of IGF-I in vivo are modulated by IGF binding proteins (IGFBPs), which generally act to inhibit IGF-I signalling. We tested the hypothesis that an analogue of IGF-I (LR IGF-I), which has significantly reduced binding affinity for IGFBPs, would improve the dystrophic pathology by reducing the susceptibility to muscle injury. Dystrophic mdx and wild-type (C57BL/10) mice were administered LR IGF-I continuously ( approximately 1.5 mg kg(-1) day(-1)) via osmotic mini-pump for 4 weeks. Administration of LR IGF-I reduced the susceptibility of extensor digitorum longus, soleus and diaphragm muscles to contraction damage, as evident from lower force deficits after a protocol of lengthening contractions. In contrast to the mechanism of protection conferred by administration of IGF-I, the protection conferred by LR IGF-I was independent of changes in muscle fatigue and oxidative metabolism. This study further indicates that modulation of IGF-I signalling has therapeutic potential for muscular diseases.},
language = {eng},
number = {11},
journal = {Experimental Physiology},
author = {Gehrig, Stefan M. and Ryall, James G. and Schertzer, Jonathan D. and Lynch, Gordon S.},
month = nov,
year = {2008},
pmid = {18567600},
keywords = {Animals, Citrate (si)-Synthase, Diaphragm, Disease Models, Animal, Infusion Pumps, Implantable, Insulin-Like Growth Factor I, Male, Mice, Mice, Inbred mdx, Muscle Contraction, Muscle Fatigue, Muscle Strength, Muscle, Skeletal, Muscular Dystrophies, Oxidative Phosphorylation, Protective Agents, Recovery of Function, Time Factors},
pages = {1190--1198},
}
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The actions of IGF-I in vivo are modulated by IGF binding proteins (IGFBPs), which generally act to inhibit IGF-I signalling. We tested the hypothesis that an analogue of IGF-I (LR IGF-I), which has significantly reduced binding affinity for IGFBPs, would improve the dystrophic pathology by reducing the susceptibility to muscle injury. Dystrophic mdx and wild-type (C57BL/10) mice were administered LR IGF-I continuously ( approximately 1.5 mg kg(-1) day(-1)) via osmotic mini-pump for 4 weeks. Administration of LR IGF-I reduced the susceptibility of extensor digitorum longus, soleus and diaphragm muscles to contraction damage, as evident from lower force deficits after a protocol of lengthening contractions. In contrast to the mechanism of protection conferred by administration of IGF-I, the protection conferred by LR IGF-I was independent of changes in muscle fatigue and oxidative metabolism. 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