Cordera R, Gherzi R, De Pirro R, Rossetti L, Freidenberg G R, Andraghetti G, Lauro R, Adezati L
Biochem Biophys Res Commun. 1985 Nov 15;132(3):991-1000. doi: 10.1016/0006-291x(85)91905-9.
The immunoglobulin G of a polyclonal antiserum (pIgG) from a patient with insulin resistance and hypoglycemia was tested for its ability to inhibit insulin binding and to affect the autophosphorylation of partially-purified insulin receptors extracted from rat liver membranes. pIgG, when added 4 hr prior to insulin, inhibited subsequent insulin binding by 50% at 30 micrograms added protein; however, insulin previously bound to the receptor could not be displaced by a 4 hr subsequent exposure of up to 70 micrograms pIgG. pIgG, independent of its effect on insulin binding, inhibited both basal and insulin-stimulated autophosphorylation of the insulin receptor in a dose-dependent manner with a half maximal effect at 3.3 to 7 micrograms protein. Furthermore, pIgG also reduced basal autophosphorylation of the EGF receptor. The effect of pIgG to inhibit basal autophosphorylation of insulin and EGF receptors, together with its ability to reduce autophosphorylation of insulin receptors fully occupied by insulin, imply that the effect of pIgG on receptor autophosphorylation is largely independent of its effect on ligand binding. Moreover, these findings suggest that pIgG may inhibit autophosphorylation by acting on domains which are similar in the insulin and EGF receptors.
对一名患有胰岛素抵抗和低血糖症患者的多克隆抗血清（pIgG）中的免疫球蛋白G进行了测试，以检测其抑制胰岛素结合的能力以及对从大鼠肝细胞膜中提取的部分纯化胰岛素受体自身磷酸化的影响。在胰岛素加入前4小时加入pIgG，当加入30微克蛋白质时，可使随后的胰岛素结合抑制50%；然而，先前与受体结合的胰岛素在随后长达4小时内暴露高达70微克pIgG时也无法被取代。pIgG无论对胰岛素结合有无影响，均以剂量依赖方式抑制胰岛素受体的基础和胰岛素刺激的自身磷酸化，在3.3至7微克蛋白质时达到半数最大效应。此外，pIgG还降低了表皮生长因子（EGF）受体的基础自身磷酸化。pIgG抑制胰岛素和EGF受体基础自身磷酸化的作用，以及其降低被胰岛素完全占据的胰岛素受体自身磷酸化的能力，表明pIgG对受体自身磷酸化的作用在很大程度上独立于其对配体结合的作用。此外，这些发现表明pIgG可能通过作用于胰岛素和EGF受体中相似的结构域来抑制自身磷酸化。
