Flier J S, Kahn C R, Jarrett D B, Roth J
J Clin Invest. 1976 Dec;58(6):1442-9. doi: 10.1172/JCI108600.
We have characterized the circulating inhibitor of insulin receptor binding found in several patients with a new syndrome of extreme insulin resistance. The inhibitor is an immunoglobulin by multiple criteria, including precipitation by 33% ammonium sulfate, migration on G-200 Sephadex gel filtration and DEAE chromatography, and immuno-precipitation with specific anti-human immuno-globulins. Although predominantly IgG, some activity is found in the IgM fraction of the immunoglobulins in one patient. The inhibitory immunoglobulins reacted with antisera to both kappa and lambda light chain determinants and are therefore polyclonal. In addition, activity is retained in the F(ab')2 fraction of pepsin-digested IgG. Evidence suggests that these antibodies are directed at determinants on or near the insulin receptor, and that they are responsible for the observed clinical insulin resistance.
我们已经对在几名患有新型极端胰岛素抵抗综合征患者中发现的胰岛素受体结合循环抑制剂进行了特征描述。根据多项标准，该抑制剂是一种免疫球蛋白，包括在33%硫酸铵中沉淀、在G-200葡聚糖凝胶过滤和DEAE色谱上的迁移，以及用特异性抗人免疫球蛋白进行免疫沉淀。虽然主要是IgG，但在一名患者的免疫球蛋白IgM部分中发现了一些活性。抑制性免疫球蛋白与抗κ和λ轻链决定簇的抗血清发生反应，因此是多克隆的。此外，胃蛋白酶消化的IgG的F(ab')2部分保留了活性。有证据表明，这些抗体针对的是胰岛素受体上或其附近的决定簇，并且它们是观察到临床胰岛素抵抗的原因。
