Grunfeld C
Proc Natl Acad Sci U S A. 1984 Apr;81(8):2508-11. doi: 10.1073/pnas.81.8.2508.
The effect of a rabbit antibody induced against the rat insulin receptor (RAR) was tested using cultured 3T3-L1 fat cells. As previously seen with antibodies against the insulin receptor from patients with the type B syndrome of insulin resistance and acanthosis nigricans, RAR acutely mimicked the action of insulin by stimulating deoxyglucose uptake. After prolonged exposure of 3T3-L1 cells to RAR, insulinomimetic activity was lost and the cells became resistant to the action of insulin. This state of insulin resistance is similar to that seen with the human autoantibodies. However, unlike antibody from the patients, RAR did not acutely inhibit the binding of insulin to its receptor; rather, RAR increased the binding of insulin to its receptor by a mechanism consistent with an increase in the affinity of the receptor for insulin. With prolonged exposure to RAR there was a dramatic decrease in insulin-receptor binding on the treated 3T3-L1 fat cells. These results suggest that antibody against the insulin receptor induces insulin resistance by a mechanism that involves loss of cell-surface insulin receptors.
利用培养的3T3-L1脂肪细胞测试了抗大鼠胰岛素受体的兔抗体（RAR）的作用。正如先前在针对患有B型胰岛素抵抗综合征和黑棘皮病患者的胰岛素受体的抗体中所观察到的那样，RAR通过刺激脱氧葡萄糖摄取急性模拟了胰岛素的作用。在3T3-L1细胞长期暴露于RAR后，胰岛素模拟活性丧失，细胞对胰岛素的作用产生抗性。这种胰岛素抵抗状态类似于在人类自身抗体中所见到的情况。然而，与患者的抗体不同，RAR不会急性抑制胰岛素与其受体的结合；相反，RAR通过一种与受体对胰岛素亲和力增加相一致的机制增加了胰岛素与其受体的结合。随着长期暴露于RAR，经处理的3T3-L1脂肪细胞上的胰岛素受体结合显著减少。这些结果表明，抗胰岛素受体抗体通过涉及细胞表面胰岛素受体丧失的机制诱导胰岛素抵抗。
