Pentoxifylline improves insulin action limiting skeletal muscle catabolismafter infection

We investigated the ability of pentoxifylline (PTX) to modulate protein syn thesis and degradation in the presence and absence of insulin during incuba tion of epitrochlearis muscle, 2 or 6 days after injection of Escherichia c oli. On days 2 and 6 after infection, protein synthesis was inhibited by 25 %, whereas proteolysis was enhanced by 75%. Insulin (2 nM) in vitro stimula ted protein synthesis in muscles from infected rats to the same extent as i n controls. The ability of insulin to limit protein degradation was severel y blunted 48 h after infection. On day 6 after infection, insulin inhibited proteolysis to a greater extent than on day 2. PTX suppressed the increase in plasma concentrations of tumor necrosis factor more than 600-fold after injection of bacteria, and partially prevented the inhibition of protein s ynthesis and stimulation of protein degradation during sepsis. Moreover, PT X administration maintained the responsiveness of protein degradation to in sulin during sepsis. Thus cytokines may influence skeletal muscle protein m etabolism during sepsis, both indirectly through inhibition of the effects of insulin on proteolysis, and directly on the protein synthesis and degrad ation machinery.