PMID: 7031662Nov 1, 1981Paper

Insulin-induced receptor loss in cultured human lymphocytes is due to accelerated receptor degradation

Proceedings of the National Academy of Sciences of the United States of America
M KasugaK M Yamada

Abstract

We have measured the turnover rate of the polypeptide subunits of the insulin receptor in cultured human lymphocytes (IM-9 line) and have investigated the mechanism of insulin-induced receptor loss. To estimate the rate of receptor degradation, lymphocytes were either pulse-labeled with [35S]methionine or surface labeled with Na125I and lactoperoxidase. The insulin receptor was isolated by immunoprecipitation with anti-receptor antibody, and the rate of loss of radioactivity from each receptor subunit was determined after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Two major (Mr 135,000 and 95,000) and one minor (Mr 210,000) subunits were found. By both labeling methods, the half-lives of the major insulin receptor subunits were 9--12 hr in normal media. When the cells were cultured in media containing 1 microM insulin the turnover was accelerated 2.5- to 3.5-fold (half-life approximately 3 hr). The increase in degradation rate was dependent on the insulin concentration and correlated well with the ability to "down-regulate" the receptor. Guinea pig insulin was about 2% as active as porcine insulin in accelerating degradation, and human growth hormone was without effect. The acceleration of receptor degradation i...Continue Reading

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Citations

Apr 1, 1984·Molecular and Cellular Biochemistry·M TrowbridgeJ Tepperman
Jan 1, 1984·Pharmacology & Therapeutics·K C Zoon, H Arnheiter
Jan 1, 1985·Pharmacology & Therapeutics·R A Roth, D O Morgan
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