INSULIN-LIKE GROWTH-FACTOR-I ACCELERATES PROTEIN-SYNTHESIS IN SKELETAL-MUSCLE DURING SEPSIS

Sepsis causes an inhibition of protein synthesis in gastrocnemius that is resistant to the anabolic effects of insulin. The purpose of the p resent studies was to investigate the effect of recombinant human insu lin-like growth factor I (IGF-I) on protein synthesis during a 30-min perfusion of the isolated rat hindlimb from septic rats. Inclusion of IGF-I (1 or 10 nM) in the perfusate stimulated protein synthesis in ga strocnemius of septic rats 2.5-fold and restored rates of protein synt hesis to those observed in control rats. The stimulation of protein sy nthesis did not result from an increase in the RNA content but was cor related with a 2.5-fold increase in the translational efficiency. The enhanced translational efficiency was accompanied by a 33 and 55% decr ease in the abundance of free 40S and 60S ribosomal subunits, respecti vely, indicating that IGF-I accelerated peptide-chain initiation relat ive to elongation/termination. These studies provide evidence that IGF -I can accelerate protein synthesis in gastrocnemius during chronic se psis by reversing the sepsis-induced inhibition of peptide-chain initi ation.