Background and aims: The PI3K protein kinase B (PI3K/Akt) signaling pathway has crucial roles in insulin signaling and other endocrine disorders. It is the purpose of this study to validate the association of PCOS with PI3K/AKT pathway target genes, miR486-5p, and miR483-5p 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 three months). The following gene expressions were assessed by real-time PCR: PI3K, AKT, ERK, GLUT4, miR486-5p, and miR483-5p in the whole blood.Result: There was a signi cant decrease in miR486-5p and miR483-5p in the PCOS group with a signi cant negative correlation between miR486-5p and PI3K and a signi cant negative correlation between miR483-5p and ERK. Metformin treatment resulted in signi cant elevation of the studied miRNAs, signi cant downregulation of PI3K/AKT target genes, and signi cant amelioration of the gonadotrophic hormonal imbalance and insulin resistance markers: fasting blood glucose, HBA1C, fasting insulin, and GLUT4 gene expression.Conclusions: miRNA486 and miRNA483 downregulation may contribute to the etiology of PCOS, in uence 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.
Highlights-PCOS is associated with multiple endocrine disorders and the most common cause is increased androgen level.-Many differentially expressed miRNAs (miR-486-5p and miR-483-5p) in PCOS women are involved in pathological insulin signaling processes, the disorder secretion of in ammatory factors, and hormones.-The most relevant genes involved in steroidogenesis, (miR-486-5p and miR-483-5p) and their controversial properties. PCOS is a complex genetic syndrome. the expression of the genes for PI3K/AKT signaling, including GLTU4, ERK, AKT, and serine/threonine kinase 1 plays a key role in the pathogenesis of PCOS.