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
Highlights
Polycystic ovary syndrome (PCOS) is a disease caused by abnormal endocrine metabolism which is characterized by ovulation dysfunction/loss, and hyperandrogenemia
leutenizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio and T levels Table 2 shows that LH, LH/FSH ratio and T levels in the model group were significantly raised, while the level of FSH was significantly low, relative to control; LH, LH/FSH ratio and T levels in inhibitor and metformin groups were significantly decreased, while FSH level was significantly raised, relative to model rats
LH, LH/FSH ratio and T levels were markedly reduced in metformin rats, relative to model rats, while FSH level was significantly raised (p < 0.05)
Summary
Polycystic ovary syndrome (PCOS) is a disease caused by abnormal endocrine metabolism which is characterized by ovulation dysfunction/loss, and hyperandrogenemia It is mainly manifested as irregular menstrual cycle, infertility, insulin resistance (IR) and polycystic ovarian changes. The tissues were bathed in ice for 30 min, during which they were repeatedly blown with a pipette to ensure complete cell lysis This was followed by centrifugation at 12000 g for 10 min, and the protein content of the supernatant was measured. Equal amounts of protein were subjected to SDS-PAGE, followed by transfer to PVDM, blocking and incubation with the appropriate primary antibodies overnight at 4oC. The number of granulosa cells and the formation of lutein were significantly improved, but were markedly reduced, when compared with the metformin group. Values of p < 0.05 were taken as indicative of statistical significance
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