Cellular mechanisms of insulin resistance in polycystic ovarian syndrome.
Cellular mechanisms of insulin resistance in polycystic ovarian syndrome.
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DOI：
10.1210/jcem.75.2.1322430
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发表时间：
1992-08
期刊：
影响因子：
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通讯作者：
T. Ciaraldi;A. El-Roeiy;Z. Madar;D. Reichart;J. Olefsky;S. Yen
中科院分区：
文献类型：
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作者：
T. Ciaraldi;A. El-Roeiy;Z. Madar;D. Reichart;J. Olefsky;S. Yen
胰岛素抵抗是多囊卵巢综合征(PCO)患者的主要特征。这种胰岛素抵抗的细胞机制尚未确定。在这项研究中，我们评估了无黑棘皮病的PCO患者(n=8)和年龄和体重匹配的对照组(n=8)分离的脂肪细胞的胰岛素作用级联反应的主要步骤、受体结合、激酶活性和葡萄糖转运活性[正常周期(NC)n=8]。PCO组为高胰岛素血症组，表现出对静脉葡萄糖负荷的胰岛素反应升高。在PCO和NC的细胞中，125I-胰岛素与脂肪细胞的结合相似。在PCO患者中，在无胰岛素的情况下，胰岛素受体亚单位的自磷酸化是正常的，但观察到胰岛素刺激的最大自磷酸化显著降低(比对照组低30%)。然而，相对于外源底物聚谷氨酸：酪氨酸(4：1)的受体激酶活性测量是正常的。在没有和存在最大胰岛素浓度的情况下，PCO受试者的细胞转运葡萄糖的速度与NC受试者相同。值得注意的是，PCO细胞转运刺激的胰岛素剂量-反应曲线有很大的右移(EC_(50)=87+/-14pmolvs.757+/-138vs.757+/-138P<0.0005)，需要8倍以上的胰岛素浓度才能达到与NC相似的葡萄糖转运速率。综上所述，我们的结果表明，在脂肪细胞中评估的PCO的胰岛素抵抗伴随着胰岛素受体的正常功能，但涉及到受体激酶和葡萄糖运输之间的胰岛素信号转导链上的新的受体后缺陷。
Insulin resistance is a predominant feature in women with polycystic ovarian syndrome (PCO). The cellular mechanisms for this insulin resistance have not been defined. In this study, major steps in the insulin action cascade, receptor binding, kinase activity, and glucose transport activity were evaluated in isolated adipocytes prepared from PCO subjects (n = 8) without acanthosis nigricans and in a group of age and weight-matched controls [normal cycling (NC) n = 8]. The PCO group was hyperinsulinemic and displayed elevated insulin responses to an iv glucose load. The binding of 125I-insulin to adipocytes was similar in cells from PCO and NC subjects. In PCO, autophosphorylation of the insulin receptor-subunit in the absence of insulin was normal but a significant decrease (30% below control) in maximal insulin stimulated autophosphorylation was observed. However, receptor kinase activity measured against the exogenous substrate poly glu:tyr (4:1) was normal. Cells from PCO subjects transported glucose at the same rate, in both the absence and presence of a maximal insulin concentration, as those from NC subjects. Strikingly, there was a large rightward shift in the insulin dose-response curve for transport stimulation in PCO cells (EC50 = 87 +/- 14 pmol in NC vs. 757 +/- 138 in PCO, P less than 0.0005); 8-fold greater insulin concentrations were required to attain comparable glucose transport rates in cells from PCO against NC. In conclusion, our results suggest that insulin resistance in PCO, as assessed in the adipocyte, is accompanied by normal function of insulin receptors, but involves a novel postreceptor defect in the insulin signal transduction chain between the receptor kinase and glucose transport.