Up- and down-regulation of insulin receptors. Kinetic models

A theoretical model for insulin receptor synthesis and degradation in differentiating 3T3-L1 adipocytes is described. This three-step irreversible ordered sequence model explains the up- and down-regulation of receptors in terms of the level of insulin concentration. Kinetic expressions were derived for the model. Numerical solutions for these equations, based on data reported by Reed and Lane (Reed, B.C., and Lane, M. D. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 285-289) were used for computer-generated curves illustrating insulin-dependent receptor synthesis and degradation. Results show that this model provides the best fit to the reported data and lend support to the suggestion that the free recycled receptor may differ from the newly synthesized receptor. A possible role for the recycled receptor in signal modulation is suggested.