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Local IGF‐I Prevents Sepsis‐Induced Muscle Atrophy
Author(s) -
Lang Charles H.,
Nystrom Gerald J.,
Frost Robert A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.991.18
Subject(s) - gastrocnemius muscle , sepsis , muscle atrophy , p70 s6 kinase 1 , medicine , endocrinology , phosphorylation , protein catabolism , inflammation , skeletal muscle , atrophy , chemistry , biochemistry , protein kinase b , amino acid
This study tests the hypothesis that local IGF‐I bioavailability regulates muscle protein balance and that muscle‐directed IGF‐I can selectively maintain muscle mass during sepsis. Increasing or decreasing bioavailable IGF‐I within muscle of mice by local injection of Leu24‐Ala31‐IGF‐I or IGFBP‐1, respectively, produced proportional changes in 4EBP1 and S6K1 phosphorylation ‐ surrogate markers of protein synthesis. In a second study, a time‐release pellet (5‐days) containing IGF‐I was implanted in the gastrocnemius and a placebo implanted in the contralateral muscle after sepsis. The gastrocnemius from septic mice with the placebo was atrophied and IGF‐I protein reduced. In contrast, local release of IGF‐I increased IGF‐I within the adjacent muscle to basal control levels, and was associated with proportional increases in muscle weight/protein. Locally‐directed IGF‐I increased the mass/protein of the exposed gastrocnemius in septic mice, and this was associated with increased phosphorylation of 4EBP1 and S6K1. Local IGF‐I selectively prevented the sepsis‐induced increase in muscle atrogin‐1 and IL‐6 mRNA. In conclusion, muscle‐directed IGF‐I prevents the characteristic sepsis‐induced atrophic response resulting from an increase in muscle protein synthesis and potentially from decreased proteolysis, without effecting metabolic processes in distant organs. (GM 38032)