Regulation of insulin receptors: evidence for involvement of an endocytotic internalization pathway
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Cultured human fibroblasts degrade insulin by a receptor-mediated process. When intracellular hormone degradation is inhibited by chloroquine, 125I-labeled insulin internalizes and accumulates intracellularly. In contrast, cultured IM-9 lymphocytes do not degrade receptor-bound insulin or accumulate 125I-labeled insulin in the presence of chloroquine. Insulin-induced receptor loss occurs in both cell types, and chloroquine inhibits this process in fibroblasts but not in IM-9 lymphocytes. Transglutaminase is a membrane-associated enzyme thought to mediate the process of ligand-induced receptor aggregation and internalization; levels of this enzyme were high in fibroblasts but barely detectable in IM-9 lymphocytes. Furthermore, dansylcadaverine--a potent inhibitor of transglutaminase--blocked insulin-induced receptor loss in fibroblasts but was without effect in IM-9 lymphocytes. These results support the concept that insulin receptor regulation is mediated via an endocytotic internalization pathway in human fibroblasts and that the mechanisms of this process differ among cell types.
author list (cited authors)
Baldwin, D., Prince, M., Marshall, S., Davies, P., & Olefsky, J. M.