Rodriguez O, Collier E, Arakaki R, Gorden P
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Metabolism. 1992 Mar;41(3):325-31. doi: 10.1016/0026-0495(92)90279-j.
Anti-insulin-receptor autoantibodies are present in the serum of patients with the type B syndrome of extreme insulin resistance. Sera from six patients with this syndrome were purified over protein-A agarose to remove insulin and other serum factors and obtain an immunoglobulin fraction. These purified fractions were used to quantitatively determine the antibodies' activity in three separate assays. The ability to inhibit insulin binding was determined in an assay using fibroblasts that overexpress the human insulin receptor; the ability to immunoprecipitate the receptor was determined in an assay using biosynthetically labeled insulin receptors rather than insulin cross-linked receptors; and the ability to stimulate glucose oxidation was determined in isolated adipocytes. We show that the ability of these antibodies to inhibit insulin binding is tightly coupled to their ability to immunoprecipitate the biosynthetically labeled receptor, but neither assay predicts the bioactivity of these immunoglobulins. We suggest that the inability to show this tight coupling in the past may be due to methodological differences. We find no evidence that these antibodies are anti-idiotypic antibodies.
抗胰岛素受体自身抗体存在于极度胰岛素抵抗B型综合征患者的血清中。来自6名患有该综合征患者的血清通过蛋白A琼脂糖进行纯化，以去除胰岛素和其他血清因子，并获得免疫球蛋白组分。这些纯化的组分用于在三种不同的检测中定量测定抗体的活性。在使用过表达人胰岛素受体的成纤维细胞的检测中测定抑制胰岛素结合的能力；在使用生物合成标记的胰岛素受体而非胰岛素交联受体的检测中测定免疫沉淀受体的能力；在分离的脂肪细胞中测定刺激葡萄糖氧化的能力。我们发现这些抗体抑制胰岛素结合的能力与其免疫沉淀生物合成标记受体的能力紧密相关，但两种检测均无法预测这些免疫球蛋白的生物活性。我们认为过去未能显示这种紧密相关性可能是由于方法学上的差异。我们没有发现证据表明这些抗体是抗独特型抗体。
