DIFFERENTIAL REGULATION OF SKELETAL-MUSCLE PROTEIN-TURNOVER BY INSULIN AND IGF-I AFTER BACTEREMIA

Skeletal muscle catabolism is a characteristic metabolic response to s epsis. We investigated the ability of physiological insulin (2 nM) or insulin-hire growth factor I (IGF-I, 10 nM) concentrations to modify p rotein metabolism during incubation of epitrochlearis 2, 6, or 15 days after injection of live Escherichia coli. On clays 2 and 6 postinfect ion, skeletal muscle exhibited an exacerbated negative protein balance resulting from both an inhibition in protein synthesis (25%) and an e nhanced proteolysis (90%) compared with controls. By day 15 postinfect ion, protein balance in infected rats was significantly improved compa red with either day 2 or 6. At this time, protein synthesis was augmen ted and protein degradation was decreased in infected rats relative to day 6. Insulin or IGF-I stimulated protein synthesis in muscles from s eptic and control rats in vitro to the same extent at each time point examined. The ability of insulin or IGF-I to Limit. protein degradatio n was severely blunted 48 h after infection. On day 6 postinfection, t he effect of insulin or IGF-I to inhibit proteolysis was more pronounc ed than on day 2. Incubation with IGF-I limited proteolysis to a great er extent than insulin on both days in infected but not control rats. By day 15, insulin diminished proteolysis to the same extent as in con trols. The results suggest that injection of bacteria causes fundament al derangements in protein metabolism that persist for days after infe ction.