Metabolic and Structural Effects of Insulin-like Growth Factor-I and High-Protein Diet on Dystrophic Hamster Skeletal Muscle

Abstract

In muscular dystrophy (MD) there is an imbalance between muscle protein synthesis and protein degradation, which results in a net muscle catabolism, along with muscle wasting and weakness. Using a dystrophic hamster model (BIO 53.58), we examined the chronic (8 weeks) effects of two factors that may enhance muscle protein synthesis and inhibit protein degradation, namely, insulin-like growth factor-I (rhlGF-I) and high-protein diet (HPD). Protein synthesis was determined by measuring the incorporation of ¹⁴C 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 rhlGF-I, HPD, or a combination of the two for 8 weeks resulted in significant decreases in total and myofibrillar degradation when compared with untreated dystrophic animals (P< 0.05) but had minimal effects on protein synthesis. Significant morphologic improvements (P< 0.05), including a normalization and greater uniformity of muscle fibers, were also seen in rhlGF-l- and rhlGF-l + HPD-treated animals. rhlGF-l and HPD were effective in reducing the excessive proteolysis seen in dystrophic muscle, and this reduced proteolysis resulted in improvement of muscle morphology.