胰岛素抵抗机制的探研——阻断型胰岛素抗体是导致胰岛素抵抗的原因之一

目的　探讨胰岛素抗体导致胰岛素抵抗发生的机制。方法　利用单抗制备技术和酶联免疫方法获得１７ 株抗人胰岛素单克隆抗体（ＭＡｂｓ） ，测定这些抗体阻断胰岛素与其受体结合、抑制ＣＨＯ 细胞（Ｃｈｉｎｅｓｅｈａｍｓｔｅｒｏｖａｒｙｃｅｌｌｓ）上胰岛素受体自身磷酸化、以及免疫结合共价交联的胰岛素胰岛素受体的能力。结果　在这组ＭＡｂｓ 中，多数ＭＡｂｓ（１６／１７）阻断胰岛素与其受体结合或抑制ＣＨＯ细胞上胰岛素受体自身磷酸化，其识别胰岛素上的位点与胰岛素的受体结合区域相重叠。有１ 株ＭＡｂ 具有免疫结合已与受体交联的胰岛素的能力，但不阻断胰岛素的作用。结论　在胰岛素抗体阳性的糖尿病患者中，其胰岛素抗体的识别位点对胰岛素抵抗的发生有重大作用。

To investigate the mechanism of insulin resistance: one of the causes for insulin resistance by blocking type insulin antibody

Objective To elucidate the mechanism of isnulin antibodies in insulin resistance. Methods A panel of 17 monoclonal antibodies (MAbs) to human insulin was produced by monoclonal antibody preparation technique and enzyme linked immunoassay. These MAbs were tested for their ability to block insulin binding to its receptor, to inhibit insulin receptor autophosphorylation in Chinese hamster ovary (CHO) cells and to immunoprecipitate insulin cross linked receptor. Results Most of MAbs in this panel (16/17) were found to block insulin binding to its receptor, to inhibit the insulin receptor's autophosphorylation in CHO cells and to recognize insulin receptor binding site on insulin. However, one MAb was able to bind insulin cross linked receptor while incapable of blocking insulin's action. Conclusion The recognition site of insulin antiobdy is important for causing insulin resistance in the diabetics with insulin antibodies.