Defects in human insulin receptor gene expression

Kaie Ojamaa, Jose A. Hedo, Charles T. Roberts, Victoria Y. Moncada, Phillip Gorden, Axel Ullrich, Simeon I. Taylor

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    30 Scopus citations

    Abstract

    The insulin receptor plays a central role in mediating the biological actions of insulin. We have used Epstein-Barr virus-transformed lymphocytes (EBV-lymphocytes) to investigate the receptor defects in patients with genetic forms of insulin resistance. Within the normal population, we found a close correlation between the number of insulin receptors on the surface of EBV-lymphocytes and the cellular content of insulin receptor mRNA. In addition, we have used the cloned human insulin receptor cDNA to investigate the nature of the mutations causing the reduction in the number of insulin receptors in EBV-lymphocytes from three insulin resistant patients. One patient with leprechaunism has a marked reduction in the level of receptor mRNA, which probably accounts for the extremely slow rate of receptor biosynthesis measured in this patient’s cells. The remaining two patients with type A extreme insulin resistance are sisters, the products of a consanguineous marriage, who have normal levels of insulin receptor mRNA. We have previously shown that the insulin receptor precursor is synthesized at a normal rate in these patients’ cells, thus suggesting a defect in the posttranslational processing of the receptor or in its translocation to the plasma membrane.

    Original languageEnglish (US)
    Pages (from-to)242-247
    Number of pages6
    JournalMolecular Endocrinology
    Volume2
    Issue number3
    DOIs
    StatePublished - Mar 1988

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    ASJC Scopus subject areas

    • Molecular Biology
    • Endocrinology

    Cite this

    Ojamaa, K., Hedo, J. A., Roberts, C. T., Moncada, V. Y., Gorden, P., Ullrich, A., & Taylor, S. I. (1988). Defects in human insulin receptor gene expression. Molecular Endocrinology, 2(3), 242-247. https://doi.org/10.1210/mend-2-3-242