IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle

Elisabeth Svanberg, Robert A. Frost, Charles H. Lang, Jorgen Isgaard, Leonard S. Jefferson, Scot R. Kimball, Thomas C. Vary

    Research output: Contribution to journalArticlepeer-review

    63 Scopus citations

    Abstract

    The present study evaluated the ability of insulin-like growth factor I (IGF-I) complexed with IGF binding protein-3 (IGFBP-3) to modulate the sepsis-induced inhibition of protein synthesis in gastrocnemius. Beginning 16 h after the induction of sepsis, either the binary complex or saline was injected twice daily via a tail vein, with measurements made 3 and 5 days later. By day 3, sepsis had reduced plasma IGF-I concentrations ~50% in saline-treated rats. Administration of the binary complex provided exogenous IGF-I to compensate for the sepsis-induced diminished plasma IGF-I. Sepsis decreased rates of protein synthesis in gastrocnemius relative to controls by limiting translational efficiency. Treatment of septic rats with the binary complex for 5 days attenuated the sepsis-induced inhibition of protein synthesis and restored translational efficiency to control values. Assessment of potential mechanisms regulating translational efficiency showed that neither the sepsis-induced change in gastrocnemius content of eukaryotic initiation factor 2B (eIF2B), the amount of eIF4E associated with 4E binding protein-1 (4E-BP1), nor the phosphorylation state of 4E-BP1 or eIF4E were altered by the binary complex. Overall, the results are consistent with the hypothesis that decreases in plasma IGF-I are partially responsible for enhanced muscle catabolism during sepsis.

    Original languageEnglish (US)
    Pages (from-to)E1145-E1158
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Volume279
    Issue number5 42-5
    DOIs
    StatePublished - 2000

    All Science Journal Classification (ASJC) codes

    • Endocrinology, Diabetes and Metabolism
    • Physiology
    • Physiology (medical)

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