Ojamaa K, Hedo J A, Roberts C T, Moncada V Y, Gorden P, Ullrich A, Taylor S I
Diabetes Branch, National Institute of Diabetes, Digestive, and Kidney Disease, Bethesda, Maryland 20892.
Mol Endocrinol. 1988 Mar;2(3):242-7. doi: 10.1210/mend-2-3-242.
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.
胰岛素受体在介导胰岛素的生物学作用中起着核心作用。我们利用爱泼斯坦-巴尔病毒转化的淋巴细胞（EBV淋巴细胞）来研究遗传性胰岛素抵抗患者的受体缺陷。在正常人群中，我们发现EBV淋巴细胞表面胰岛素受体的数量与胰岛素受体mRNA的细胞含量之间存在密切相关性。此外，我们使用克隆的人胰岛素受体cDNA来研究导致三名胰岛素抵抗患者的EBV淋巴细胞中胰岛素受体数量减少的突变性质。一名患有妖精貌综合征的患者受体mRNA水平显著降低，这可能是该患者细胞中测得的受体生物合成速率极慢的原因。其余两名患有A型极端胰岛素抵抗的患者是近亲结婚的姐妹，她们的胰岛素受体mRNA水平正常。我们之前已经表明，这些患者细胞中胰岛素受体前体的合成速率正常，因此提示受体的翻译后加工或其向质膜的转运存在缺陷。
