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

Abstract

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-linkedassay (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.
 Keywords: Metformin, Polycystic ovary syndrome, Leutenizing hormone, Insulin resistance, Fasting blood sugar, Follicle-stimulating hormone

Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport

“…Another study using the rat PCOS model demonstrated a significant reduction in IRS2 and PI3K expression, and 4-week in vivo metformin treatment significantly increased their expression [74]. Furthermore, in an additional study, reduced PI3K and Akt expression observed in ovarian and hepatic tissues of the rat PCOS model increased significantly after metformin treatment [75]. In a study by Ferreira et al, both metformin and insulin increased PI3K and GLUT4 expression in endometrial cell culture, and their combined effect was even more pronounced [67].…”

SGLT‐2 inhibitors enhance the effect of metformin to ameliorate hormonal changes and inflammatory markers in a rat PCOS model

“…Previous studies have shown the beneficial impact of metformin on hormonal disturbances in PCOS; A study by Hu et al. (2020) on the impact of metformin on PCOS in rats revealed that metformin‐treated animals had significantly improved levels of LH, testosterone, FSH, and LH/FSH ratio compared to model rats. They also showed that the number of granulosa cells and the production of lutein were significantly improved in the metformin‐treated group, while cystic follicle enlargement was missing.…”