METABOLIC AND STRUCTURAL EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I AND HIGH-PROTEIN DIET ON DYSTROPHIC HAMSTER SKELETAL-MUSCLE

In muscular dystrophy (MD) there is an imbalance between muscle protei n synthesis and protein degradation, which results in a net muscle cat abolism, along with muscle wasting and weakness. Using a dystrophic ha mster model (BIO 53.58), we examined the chronic (8 weeks) effects of two factors that may enhance muscle protein synthesis and inhibit prot ein degradation, namely, insulin-like growth factor-I (rhIGF-I) and hi gh-protein diet (HPD). Protein synthesis was determined by measuring t he incorporation of C-14 phenylalanine into perfused leg muscle, while protein degradation was calculated from the release of tyrosine from the same perfused muscle. Urinary 3-methylhistidine excretion was used as an indicator of myofibrillar degradation. Treatment of dystrophic hamsters with rhIGF-I, HPD, or a combination of the two for 8 weeks re sulted in significant decreases in total and myofibrillar degradation when compared with untreated dystrophic animals (P < 0.05) but had min imal effects on protein synthesis. Significant morphologic improvement s (P < 0.05), Including a normalization and greater uniformity of musc le fibers, were also seen in rhIGF-I- and rhIGF-I + HPD-treated animal s. rhIGF-I and HPD were effective in reducing the excessive proteolysi s seen in dystrophic muscle, and this reduced proteolysis resulted in improvement of muscle morphology.