EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I IN MURINE MUSCULAR-DYSTROPHY

In muscular dystrophy there is an imbalance between muscle protein syn thesis and protein degradation, resulting in net muscle catabolism and progressive muscle weakness and wasting. Both insulin and insulin-lik e growth factor I (IGF-I) are known to have an anabolic effect on skel etal muscle, which is believed to be enhanced in the presence of eleva ted concentrations of amino acids. We examined the effects of 4-week a dministration of recombinant human IGF-I (rhIGF-I), both alone and sup plemented with a high protein diet (HPD), on muscle metabolism, morpho logy, and function in the 129 ReJ dystrophic mouse. rhIGF-I significan tly reduced muscle protein degradation (P < 0.001), increased muscle p rotein content (P < 0.05), decreased fiber area variability (P < 0.01) , and increased hind limb utilization (P < 0.01). Supplementation of r hIGF-I therapy with a HPD resulted in a significant increase in muscle protein synthesis (P < 0.05) in addition to a further increase in the above parameters. We conclude that rhIGF-I causes an improvement in m uscle metabolism, morphology, and function in dystrophic mice, and thi s effect is further enhanced by the presence of a HPD.