Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls
Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls
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DOI：
10.1507/endocrj.ej13-0423
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发表时间：
2014-02-01
影响因子：
2
通讯作者：
Larner, Joseph
中科院分区：
文献类型：
--
作者：
Heimark, Douglas;McAllister, Jan;Larner, Joseph
我们和其他实验室先前的研究表明，胰岛素抵抗与肌醇失衡有关，体内和体外均存在肌醇过剩和肌醇缺乏，以及肌醇对肌醇外聚酶的缺乏。在本报告中，我们利用胰岛素敏感性正常的正常周期女性的卵膜细胞和胰岛素敏感性增加的多囊卵巢综合征（PCOS）女性的卵膜细胞来检测肌醇/肌醇（M/C）比率和肌醇/肌醇epimase活性。胰岛素敏感性增加的多囊卵巢综合征（PCOS）卵泡细胞被专门用于研究肌醇失衡和肌醇向肌醇epimase的转变是否与胰岛素抵抗细胞的调节方向相似或相反。这些研究的结果首次证明，在胰岛素敏感的多囊卵巢综合征（PCOS）细胞中，肌醇失衡的方向与胰岛素抵抗细胞相反，M/C比率下降，肌肌醇与肌醇epimase活性增加。进一步的生物化学和遗传学研究将探讨其中的机制。
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.