Insulin receptor sub-types in a human lymphoid-derived cell line (IM-9): differential regulation by insulin, dexamethasone and monensin.

The cells of the human IM-9 lymphocyte-derived line contain a subpopulation of insulin binding sites which differ from classical insulin binding sites in their higher binding affinity for insulin-like growth factor II (IGF-II) and insulin-like growth factor I (IGF-I). These atypical insulin binding sites are identified on IM-9 cells by [125I]IGF-II binding. To determine whether the atypical and classical insulin receptors of IM-9 cells were subject to different modes of in vivo regulation, we treated IM-9 cells with agents known to alter the surface expression of insulin receptors--insulin, dexamethasone and monensin. We then measured insulin and IGF-II binding to the surface of the washed cells. Pretreatment of IM-9 cells with 1 microM insulin for 20 h at 37 degrees C induced a 44-48% decrease in the number of high affinity insulin binding sites, but no change in the number of IGF-II binding sites. In contrast, the surface expression of both insulin and IGF-II binding sites (classical and atypical insulin receptors) increased 1.3 to 1.7-fold after treatment with dexamethasone (200 nM) and decreased 30 to 45% after monensin (1 microM). These results suggest that atypical and classical insulin receptors are differentially susceptible to down-regulation by insulin.