Flier J S, Kahn C R, Jarrett D B, Roth J
J Clin Invest. 1977 Oct;60(4):784-94. doi: 10.1172/JCI108832.
The serum of some patients with insulin-resistant "diabetes" contains antibodies that bind to and block the cell membrane receptors for insulin. In this report, we have characterized the effects of the antireceptor antibodies on the interaction of (125)I-insulin with its receptor on the human lymphoblastoid cell line IM-9. Up to 95% of specific insulin binding can be inhibited by pretreatment of the cells with these immunoglobulins. The onset of the inhibitory effect is time- and temperature-dependent, and the effect is reversed extremely slowly if the cells are suspended in a large excess of antibody-free buffer. These features of antibody binding can be easily distinguished from those for insulin binding to its receptor. The inhibitory effect of the antibodies can be reversed by exposure of the cells to conditions known to elute surface immunoglobulins. The three antireceptor sera studied appear to alter the insulin-receptor interaction in different ways. Two antisera markedly reduce receptor affinity through combined effects on the insulin association and dissociation rates, and, additionally, have smaller effects on available receptor number. A third antiserum primarily affects available receptor number and has little effect on receptor affinity. All three antisera inhibit the capacity of insulin to promote negatively cooperative site-site interactions among insulin receptors. The data suggest that these autoantibodies to the insulin receptor bind to different determinants on the receptor and may therefore be useful as unique probes of insulin receptor structure and function.
一些患有胰岛素抵抗性“糖尿病”的患者血清中含有能与胰岛素细胞膜受体结合并阻断该受体的抗体。在本报告中，我们已对这些抗受体抗体对（125）I -胰岛素与其在人淋巴母细胞系IM - 9上的受体相互作用的影响进行了表征。用这些免疫球蛋白预处理细胞可抑制高达95%的特异性胰岛素结合。抑制作用的起始具有时间和温度依赖性，并且如果将细胞悬浮在大量无抗体缓冲液中，该作用逆转极其缓慢。抗体结合的这些特征可轻易与胰岛素与其受体结合的特征区分开来。通过将细胞暴露于已知能洗脱表面免疫球蛋白的条件下，可逆转抗体的抑制作用。所研究的三种抗受体血清似乎以不同方式改变胰岛素 - 受体相互作用。两种抗血清通过对胰岛素结合和解离速率的综合作用显著降低受体亲和力，此外，对可用受体数量的影响较小。第三种抗血清主要影响可用受体数量，对受体亲和力影响较小。所有三种抗血清均抑制胰岛素促进胰岛素受体之间负协同位点 - 位点相互作用的能力。数据表明，这些针对胰岛素受体的自身抗体与受体上不同的决定簇结合，因此可能作为胰岛素受体结构和功能的独特探针。
