Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital, University of Chile, Santiago, Chile.
Department of Bioanalysis and Immunology, Faculty of Sciences, National Autonomous University of Honduras, Tegucigalpa, Honduras.
Am J Physiol Endocrinol Metab. 2020 Feb 1;318(2):E237-E248. doi: 10.1152/ajpendo.00162.2019. Epub 2019 Dec 24.
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder characterized by hyperandrogenism and ovulatory dysfunction but also obesity and hyperinsulinemia. These characteristics induce an insulin-resistant state in tissues such as the endometrium, affecting its reproductive functions. Myo-inositol (MYO) is an insulin-sensitizing compound used in PCOS patients; however, its insulin-sensitizing mechanism is unclear. To understand the relationship of MYO with insulin action in endometrial cells, sodium/myo-inositol transporter 1 (SMIT-1) (MYO-transporter), and MYO effects on protein levels related to the insulin pathway were evaluated. SMIT-1 was assessed in endometrial tissue from women with normal weight, obesity, insulin resistance, and PCOS; additionally, using an in vitro model of human endometrial cells exposed to an environment resembling hyperinsulinemic-obese-PCOS, MYO effect was evaluated on p-AMPK and GLUT-4 levels and glucose uptake by Western blot, immunocytochemistry, and confocal microscopy, respectively. SMIT-1 was detected in endometrial tissue from all groups and decreased in PCOS and obesity ( < 0.05 vs. normal weight In the in vitro model, PCOS conditions decreased p-AMPK levels, while they were restored with MYO ( < 0.05). The diminished GLUT-4 protein levels promoted by PCOS environment were restored by MYO through SMIT-1 and p-AMPK-dependent mechanism ( < 0.05). Also, MYO restored glucose uptake in cells under PCOS condition through a p-AMPK-dependent mechanism. Finally, these results were similar to those obtained with metformin treatment in the same in vitro conditions. Consequently, MYO could be a potential insulin sensitizer through its positive effects on insulin-resistant tissues as PCOS-endometrium, acting through SMIT-1, provoking AMPK activation and elevated GLUT-4 levels and, consequently, increase glucose uptake by human endometrial cells. Therefore, MYO may be used as an effective treatment option in insulin-resistant PCOS women.
多囊卵巢综合征（PCOS）是一种内分泌代谢紊乱疾病，其特征是高雄激素血症和排卵功能障碍，但也与肥胖和高胰岛素血症有关。这些特征会导致子宫内膜等组织出现胰岛素抵抗状态，影响其生殖功能。肌醇（MYO）是一种用于治疗 PCOS 患者的胰岛素增敏化合物；然而，其胰岛素增敏机制尚不清楚。为了了解 MYO 与子宫内膜细胞胰岛素作用的关系，评估了钠/肌醇转运蛋白 1（SMIT-1）（MYO 转运蛋白）和 MYO 对胰岛素通路相关蛋白水平的影响。评估了来自体重正常、肥胖、胰岛素抵抗和 PCOS 妇女的子宫内膜组织中的 SMIT-1；此外，使用体外人子宫内膜细胞模型暴露于类似于高胰岛素血症-肥胖-PCOS 的环境中，通过 Western blot、免疫细胞化学和共聚焦显微镜分别评估 MYO 对 p-AMPK 和 GLUT-4 水平以及葡萄糖摄取的影响。在所有组的子宫内膜组织中均检测到 SMIT-1，并且在 PCOS 和肥胖中减少（<0.05 与体重正常相比）。在体外模型中，PCOS 条件降低了 p-AMPK 水平，而 MYO 则恢复了（<0.05）。PCOS 环境下降低的 GLUT-4 蛋白水平通过 MYO 依赖于 SMIT-1 和 p-AMPK 的机制得到恢复（<0.05）。此外，MYO 通过 p-AMPK 依赖的机制恢复了 PCOS 条件下细胞的葡萄糖摄取。最后，这些结果与在相同体外条件下用二甲双胍治疗获得的结果相似。因此，MYO 可以通过对 PCOS 子宫内膜等胰岛素抵抗组织的积极作用成为一种潜在的胰岛素增敏剂，通过 SMIT-1 引起 AMPK 激活和升高 GLUT-4 水平，从而增加人子宫内膜细胞的葡萄糖摄取。因此，MYO 可作为胰岛素抵抗性 PCOS 妇女的有效治疗选择。
