Pentoxifylline improves insulin action limiting skeletal muscle catabolism after infection

• Published in: Journal of endocrinology Vol. 163; no. 1; pp. 15 - 24
• Main Authors: Vary, T, Dardevet, D, Grizard, J, Voisin, L, Buffiere, C, Denis, P, Breuille, D, Obled, C
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.10.1999; Portland Press
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Culture Techniques; Endocrinology and metabolism; Escherichia coli Infections - drug therapy; Escherichia coli Infections - metabolism; Forelimb; General aspects; Human health and pathology; Infection pathogenesis; Infectious diseases; Insulin - therapeutic use; Life Sciences; Male; Medical sciences; Muscle Proteins - biosynthesis; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Pentoxifylline - therapeutic use; Phenylalanine - metabolism; Phosphodiesterase Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha - metabolism; Tyrosine - metabolism; Pancreatic hormone; 3',5'-Cyclic-nucleotide phosphodiesterase; Rat; Enzyme; Cytokine; Rodentia; Enzyme inhibitor; Esterases; Phosphoric diester hydrolases; Metabolism; Striated muscle; Insulin; Protein; Infection; Pentoxifylline; Vertebrata; Experimental disease; Mammalia; Animal; Hydrolases; Catabolism; Xanthine derivatives; Tumor necrosis factor α
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1630015

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.