Forsayeth J R, Caro J F, Sinha M K, Maddux B A, Goldfine I D
Proc Natl Acad Sci U S A. 1987 May;84(10):3448-51. doi: 10.1073/pnas.84.10.3448.
Three mouse monoclonal antibodies were produced that reacted with the alpha subunit of the human insulin receptor. All three both immunoprecipitated 125I-labeled insulin receptors from IM-9 lymphocytes and competitively inhibited 125I-labeled insulin binding to its receptor. Unlike insulin, the antibodies failed to stimulate receptor autophosphorylation in both intact IM-9 lymphocytes and purified human placental insulin receptors. Moreover, unlike insulin, the antibodies failed to stimulate receptor-mediated phosphorylation of exogenous substrates. However, like insulin, two of the three antibodies stimulated glucose transport in isolated human adipocytes. One antibody, on a molar basis, was as potent as insulin. These studies indicate, therefore, that monoclonal antibodies to the insulin receptor can mimic a major function of insulin without activating receptor kinase activity. They also raise the possibility that certain actions of insulin such as stimulation of glucose transport may not require the activation of receptor kinase activity.
制备了三种与人类胰岛素受体α亚基发生反应的小鼠单克隆抗体。这三种抗体都能从IM-9淋巴细胞中免疫沉淀125I标记的胰岛素受体，并竞争性抑制125I标记的胰岛素与其受体的结合。与胰岛素不同，这些抗体在完整的IM-9淋巴细胞和纯化的人胎盘胰岛素受体中均未能刺激受体自身磷酸化。此外，与胰岛素不同，这些抗体未能刺激受体介导的外源底物磷酸化。然而，与胰岛素一样，三种抗体中的两种能刺激分离的人脂肪细胞中的葡萄糖转运。其中一种抗体，按摩尔计算，与胰岛素的效力相当。因此，这些研究表明，针对胰岛素受体的单克隆抗体可以模拟胰岛素的主要功能，而无需激活受体激酶活性。它们还增加了胰岛素的某些作用（如刺激葡萄糖转运）可能不需要激活受体激酶活性的可能性。
