Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, Cairo, 11562, Egypt.
Obstetrics and Gynecology Department, Faculty of Medicine, Minia University, Minya, Egypt.
Mol Biol Rep. 2023 Oct;50(10):8361-8372. doi: 10.1007/s11033-023-08604-0. Epub 2023 Aug 24.
The PI3K protein kinase B (PI3K/AKT) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. The purpose of this study is to validate the association of PCOS with PI3K/AKT pathway target genes, miRNA486-5p, and miRNA483-5p as well as to evaluate the outcome of metformin on the pathogenesis of PCOS. METHODS: This case-controlled study included 3 subject groups: twenty healthy females (control group), twenty PCOS females before treatment, and twenty PCOS females treated with metformin at a dose (500 mg 3 times per day for 3 months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miRNA486-5p, and miRNA483-5p in the whole blood.
There was a significant decrease in miRNA486-5p and miRNA483-5p in the PCOS group with a significant negative correlation between miRNA486-5p and PI3K and a significant negative correlation between miRNA483-5p and ERK. Metformin treatment resulted in significant elevation of the studied miRNA, significant downregulation of PI3K/AKT target genes, and significant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression.
miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, influence glucose metabolism, and result in IR in PCOS. Metformin's upregulation of those miRNAs affects glucose metabolism by controlling the expression of GLUT4, ameliorates PCOS-related insulin resistance, and improves PCOS-related hormonal imbalance by controlling the PI3K/AKT signaling pathway.
PI3K 蛋白激酶 B（PI3K/AKT）信号通路在胰岛素信号和其他内分泌紊乱中具有关键作用。本研究旨在验证 PCOS 与 PI3K/AKT 通路靶基因、miRNA486-5p 和 miRNA483-5p 的关联，并评估二甲双胍对 PCOS 发病机制的影响。
本病例对照研究纳入了 3 个研究组：20 名健康女性（对照组）、20 名未经治疗的 PCOS 女性和 20 名接受二甲双胍治疗（500mg，每日 3 次，治疗 3 个月）的 PCOS 女性。采用实时 PCR 评估以下基因在全血中的表达：PI3K、AKT、ERK、GLUT4、miRNA486-5p 和 miRNA483-5p。
PCOS 组的 miRNA486-5p 和 miRNA483-5p 显著下降，miRNA486-5p 与 PI3K 呈显著负相关，miRNA483-5p 与 ERK 呈显著负相关。二甲双胍治疗导致研究的 miRNA 显著升高，PI3K/AKT 靶基因显著下调，促性腺激素失衡和胰岛素抵抗标志物：空腹血糖、HBA1C、空腹胰岛素和 GLUT4 基因表达显著改善。
miRNA486 和 miRNA483 的下调可能导致 PCOS 的发病机制，影响葡萄糖代谢，并导致 PCOS 中的 IR。二甲双胍对这些 miRNA 的上调通过控制 GLUT4 的表达来影响葡萄糖代谢，改善与 PCOS 相关的胰岛素抵抗，并通过控制 PI3K/AKT 信号通路改善与 PCOS 相关的激素失衡。
