Pentoxifylline improves insulin action limiting skeletal muscle catabolism after infection.
We investigated the ability of pentoxifylline (PTX) to modulate protein synthesis and degradation in the presence and absence of insulin during incubation of epitrochlearis muscle, 2 or 6 days after injection of Escherichia coli. On days 2 and 6 after infection, protein synthesis was inhibited by 25%, whereas proteolysis was enhanced by 75%. Insulin (2 nM) in vitro stimulated protein synthesis in muscles from infected rats to the same extent as in controls. The ability of insulin to limit protein degradation was severely 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 synthesis and stimulation of protein degradation during sepsis. Moreover, PTX administration maintained the responsiveness of protein degradation to insulin during sepsis. Thus cytokines may influence skeletal muscle protein metabolism during sepsis, both indirectly through inhibition of the effects of insulin on proteolysis, and directly on the protein synthesis and degradation machinery.
Vary
T
T
Laboratoire d'Etude du Metabolisme Azote, Institut National de la Recherche Agronomique, Theix 63122 Ceyrat, France.
Dardevet
D
D
Grizard
J
J
Voisin
L
L
Buffiere
C
C
Denis
P
P
Breuille
D
D
Obled
C
C
D000704:Analysis of Variance; D000818:Animals; D046508:Culture Techniques; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism*; D005552:Forelimb; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010431:Pentoxifylline / Q000627:therapeutic use*; D010649:Phenylalanine / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D009124:Muscle Proteins; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D010649:Phenylalanine; D010431:Pentoxifylline