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Effect of insulin upon protein degradation in cultured human myocytes
Author(s) -
Roberts R. G.,
Redfern C. P. F.,
Goodship T. H. J.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01226.x
Subject(s) - ubiquitin , insulin , protein degradation , myocyte , insulin degrading enzyme , catabolism , anabolism , medicine , endocrinology , skeletal muscle , insulin receptor , proteolysis , biology , chemistry , enzyme , biochemistry , metabolism , insulin resistance , gene
Background The anabolic effects of insulin are well recognized but the mechanism by which insulin decreases muscle protein degradation in human is unclear. However, in a variety of catabolic conditions it is believed to be changes in the activity of the ATP‐dependent ubiquitin proteolytic pathway that are responsible for changes in protein degradation in skeletal muscle. The aim of this study was to test the hypothesis that insulin regulates the ATP‐dependent ubiquitin proteolytic pathway in human muscle. Material and methods The effects of insulin and acidosis on protein degradation were measured in human myocytes using L‐[ 14 C]phenylalanine. The effect of insulin on the activity of the ATP‐dependent ubiquitin pathway was assessed from the mRNA expression of ubiquitin and the ubiquitin‐conjugating enzyme E2 14k in human myocytes. Results and conclusions Coincubation of human myocytes with 100 nM of insulin was associated with a significant reduction in protein degradation. Metabolic acidosis is known to increase skeletal muscle protein degradation rates, and in our experiments protein degradation at a pH of 7·0 was significantly higher than pH 7·35. Eight‐hour exposure to 100 nM of insulin resulted in a significant reduction in the expression of E2 14k but no change in the expression of ubiquitin. Conclusions In human muscle we have demonstrated regulation by insulin of the ATP‐dependent ubiquitin pathway at the level of ubiquitin conjugation.