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在患有多囊性卵巢综合征(PCO)的妇女中,胰岛素抵抗是一个显著的特征。其细胞水平机制尚未明确。本研究从无黑棘皮症PCO患者(n=8)及年龄与体重匹配的正常对照[正常周期(NC)n=8]中分离的脂肪细胞,评价胰岛素作用链中的主要步骤:受体结合,激酶作用及葡萄糖转运功能。PCO组血胰岛素升高,在静脉葡萄糖负荷吋胰岛素反应增强。~(125)I-胰岛素与PCO和NC的脂肪细胞的结合相似。PCO中胰岛素受体亚基的自身磷酸化在无胰岛素时是正常的,但观察到在最大胰岛素刺激时自身磷酸化显著下降(低于对照30％)。然而,对外源性底物多聚谷氨酸:酪氨酸(4∶1)所测得的受体激酶活性是正常的。在无或有最大浓度胰岛素两种情况下,PCO的细胞转运葡萄糖的速度与NC组相同:引人注目的是.PCO细胞中刺激转运的胰岛素剂量-反应曲线大幅度右移(NC中EC_(50)=87±14pmol,而PCO中为757±138Pmol,P<0.0005)。在PCO细胞中,要获得与NC组相似的葡萄糖转运率,需要8倍多的胰岛素浓度。结论:我们的结果提示从脂肪细胞估计PCO中的胰岛素抵抗,伴有正常功能的胰岛素受体,但在受体激酶和葡萄糖转运之间的链中存在一种新的受体后缺陷。
In women with polycystic ovary syndrome (PCO), insulin resistance is a significant feature. The mechanism of cell level is not yet clear. In this study, adipocytes isolated from patients with acanthosis nigricans (n = 8) and age-matched normal controls [normal nocturnal (NC) n = 8] were used to assess the major steps in the insulin action chain: receptor binding , Kinase function and glucose transport function. Insulin was elevated in the PCO group and increased in the venous glucose load. The binding of ~ (125) I-insulin to adipocytes of PCO and NC is similar. Autophosphorylation of the insulin receptor subunit in PCO was normal in the absence of insulin, but a significant decrease in autophosphorylation was observed at maximal insulin stimulation (30% below control). However, the receptor kinase activity measured for the exogenous substrate polyglutamic acid: tyrosine (4: 1) is normal. In both no or maximal concentrations of insulin, PCO cells transported glucose at the same rate as the NC group: notably, the insulin-dose-response curve stimulating transport in PCO cells shifted to the right (NC in EC_ ( 50) = 87 ± 14 pmol versus 757 ± 138 Pmol in PCO, P <0.0005). In PCO cells, to obtain glucose transport rates similar to those in the NC group, an 8-fold more insulin concentration was required. CONCLUSIONS: Our results suggest that insulin resistance in PCO is estimated from adipocytes with a normally functioning insulin receptor, but there is a new post-receptor defect in the chain between receptor kinase and glucose transport.