Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia

• Published in: American journal of physiology: endocrinology and metabolism 1998-10, Vol.275 (4), p.E584-E593
• Main Authors: Vary, Thomas C, Dardevet, Dominique, Grizard, Jean, Voisin, Laure, Buffiere, Caroline, Denis, Phillipe, Breuille, Denis, Obled, Christiane
• Format: Article
• Language: English
• Subjects: Endocrinology and metabolism; Human health and pathology; Life Sciences
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.1998.275.4.e584

Laboratoire d'Etude du Metabolisme Azote, Institut National de la Recherche Agronomique, Theix 63122 Ceyrat; Clintec Technologies, 78148 Velizy Cedex, France; and Department of Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 10733 Skeletal muscle catabolism is a characteristic metabolic response to sepsis. We investigated the ability of physiological insulin (2 nM) or insulin-like growth factor I (IGF-I, 10 nM) concentrations to modify protein metabolism during incubation of epitrochlearis 2, 6, or 15 days after injection of live Escherichia coli . On days 2  and 6  postinfection, skeletal muscle exhibited an exacerbated negative protein balance resulting from both an inhibition in protein synthesis (25%) and an enhanced proteolysis (90%) compared with controls. By day 15  postinfection, protein balance in infected rats was significantly improved compared with either day 2  or 6 . At this time, protein synthesis was augmented and protein degradation was decreased in infected rats relative to day 6 . Insulin or IGF-I stimulated protein synthesis in muscles from septic and control rats in vitro to the same extent at each time point examined. The ability of insulin or IGF-I to limit protein degradation was severely blunted 48 h after infection. On day 6  postinfection, the effect of insulin or IGF-I to inhibit proteolysis was more pronounced than on day 2 . Incubation with IGF-I limited proteolysis to a greater extent than insulin on both days in infected but not control rats. By day 15 , insulin diminished proteolysis to the same extent as in controls. The results suggest that injection of bacteria causes fundamental derangements in protein metabolism that persist for days after infection. epitrochlearis; protein synthesis; proteolysis; insulin-like growth factor I; sepsis