IGF-I STIMULATES PROTEIN-SYNTHESIS BUT DOES NOT INHIBIT PROTEIN BREAKDOWN IN MUSCLE FROM SEPTIC RATS

Sepsis is associated with reduced protein synthesis and increased prot ein degradation in skeletal muscle. We examined the effects of insulin -like growth factor I (IGF-I) on protein synthesis and breakdown in mu scles from nonseptic and septic rats. Sepsis was induced by cecal liga tion and puncture; control rats were sham operated. Extensor digitorum longus muscles were incubated in the absence or presence of IGF-I at concentrations ranging from 100 ng/ml to 10 mu g/ml. Total and myofibr illar protein breakdown rates were measured as net release of tyrosine and 3-methylhistidine, respectively. Protein synthesis was determined by measuring incorporation of [U-C-14]phenylalanine into protein. IGF -I stimulated protein synthesis in a dose-dependent fashion in muscles from both sham-operated and septic rats, with a maximal effect seen a t a hormone concentration between 500 and 1,000 ng/ml. IGF-I inhibited total and myofibrillar protein breakdown in muscles from sham-operate d rats, whereas in muscles from septic rats, IGF-I had no effect on pr otein breakdown, even at high concentrations. The results suggest that protein breakdown in skeletal muscle becomes resistant to IGF-I durin g sepsis and that this resistance reflects a postreceptor defect.