Mitigating effect of metformin on polycystic ovarian syndrome and insulin resistance in rats, and the mechanisms involved

Purpose: To study the effect of metformin on polycystic ovarian syndrome (PCOS) and insulin resistance (IR) in rats, and the mechanism involved. Methods: Eighty healthy female SD rats, aged 6 weeks, were selected. Three groups of rats were used: model, metformin + PI3K inhibitor, and metformin groups, with 20/group. Testosterone, leutenizing hormone (LH), and follicle-stimulating hormone (FSH) were assayed by enzyme-linked assay (ELISA), while HOMA-IR was calculated from fasting blood sugar (FBG); the effect of metformin on the IR of PCOS rats was determined. The expressions of PI3K and AKT in ovaries and liver of rats in each group were assayed by Western blotting. Results: Fasting blood glucose, fasting insulin, and insulin resistance index were markedly higher in model than in control rats, and also significantly higher in inhibitor-treated rats than in metformin rats (p < 0.05). Relative to control, FSH level was higher, while levels of LH, LH/FSH ratio and testosterone in the metformin group were significantly lower (p < 0.05). The expression levels of PI3K and AKT in the ovary and liver were reduced in the inhibitor group, relative to the levels in metformin-treated rats (p < 0.05). Conclusion: Metformin mitigates PCOS-linked ovarian changes and IR in rats via PI3K/AKT route. These findings may be useful in the design of new drugs.