Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage.

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.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Gehrig SM,Ryall JG,Schertzer JD,Lynch GS

doi

10.1113/expphysiol.2008.042838

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

1190-8

issue

11

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2008.042838

journal_volume

93

pub_type

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