Heimark Douglas, McAllister Jan, Larner Joseph
Department of Pharmacology, University of Virginia, Charlottesville, VA 22903 USA.
Endocr J. 2014;61(2):111-7. doi: 10.1507/endocrj.ej13-0423. Epub 2013 Nov 2.
Previous studies from our and other labs have shown that insulin resistance is associated with an inositol imbalance of excess myo-inositol and deficient chiro-inositol together with a deficiency of myo-inositol to chiro-inositol epimerase in vivo and in vitro. In this report, we utilized well characterized theca cells from normal cycling women, with normal insulin sensitivity, and theca cells from women with polycystic ovary syndrome (PCOS), with increased insulin sensitivity to examine the myo-inositol to chiro-inisitol (M/C) ratio and the myo-inositol to chiro-inositol epimerase activity. PCOS theca cells with increased insulin sensitivity were specifically used to investigate whether the inositol imbalance and myo-inositol to chiro-inositol epimerase are regulated in a similar or the opposite direction than that observed in insulin resistant cells. The results of these studies are the first to demonstrate that in insulin sensitive PCOS theca cells the inositol imbalance goes in the opposite direction to that observed in insulin resistant cells, and there is a decreased M/C ratio and an increased myo-inositol to chiro-inositol epimerase activity. Further biochemical and genetic studies will probe the mechanisms involved.
我们实验室和其他实验室之前的研究表明，胰岛素抵抗与肌醇失衡有关，即体内和体外均存在肌醇过量、手性肌醇缺乏以及肌醇向手性肌醇差向异构酶缺乏的情况。在本报告中，我们利用来自正常月经周期女性且胰岛素敏感性正常的特征明确的卵泡膜细胞，以及来自多囊卵巢综合征（PCOS）女性且胰岛素敏感性增加的卵泡膜细胞，来检测肌醇与手性肌醇（M/C）的比例以及肌醇向手性肌醇差向异构酶的活性。具有增加胰岛素敏感性的PCOS卵泡膜细胞被专门用于研究肌醇失衡和肌醇向手性肌醇差向异构酶是否与胰岛素抵抗细胞中的调节方向相似或相反。这些研究结果首次表明，在胰岛素敏感的PCOS卵泡膜细胞中，肌醇失衡与胰岛素抵抗细胞中的方向相反，M/C比例降低，肌醇向手性肌醇差向异构酶活性增加。进一步的生化和遗传学研究将探究其中涉及的机制。
