INSULIN-LIKE-GROWTH-FACTOR-1 STIMULATES PROTEIN-SYNTHESIS AND INHIBITS PROTEIN BREAKDOWN IN MUSCLE FROM BURNED RATS

Background: Burn injury is associated with substantial whole-body prot ein loss, reflecting mainly a catabolic response in skeletal muscle. R ecent studies suggest that treatment with insulin-like growth factor 1 (IGF-1) may reverse the catabolic response to burn injury, but the ef fects of IGF-1 on muscle protein synthesis and breakdown rates after b urn injury are not known. We tested the hypothesis that IGF-1 blunts t he catabolic response in skeletal muscle after burn injury by stimulat ing protein synthesis and inhibiting protein breakdown and that this e ffect of IGF-I is caused by a direct effect on muscle tissue. Methods: Intact extensor digitorum longus muscles from burned, sham-burned, an d untreated rats were incubated in the absence or presence of differen t concentrations of IGF-1. Total and myofibrillar protein breakdown ra tes were measured as net release of tyrosine and 3-methylhistidine, re spectively. Protein synthesis rates were determined by measuring the i ncorporation of (U-C-14)-phenylalanine into protein. Results: IGF-1 st imulated protein synthesis and inhibited protein breakdown in a dose-d ependent fashion in muscles from burned and unburned rats. The maximal effect of IGF-1 on protein synthesis was seen at a hormone concentrat ion of 100 ng/mL, whereas protein breakdown was further inhibited when the hormone concentration was increased to 1 mu g/mL. Ubiquitin messe nger RNA (mRNA) levels were reduced by IGF-1 in incubated muscles, sug gesting that IGF-1 may inhibit ubiquitin-dependent protein breakdown. Conclusions: These results suggest that the anabolic effects of IGF-1 after burn may reflect inhibited protein breakdown and stimulated prot ein synthesis in skeletal muscle and that this response may be caused by a direct effect of IGF-1 on muscle tissue.