Effects of metformin and Exenatide on insulin resistance and AMPK[alpha]-SIRT1 molecular pathway in PCOS rats

Aims This study was designed to evaluate the protective effects of AMPK[alpha] and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. Methods An in vitro PCOS model was established by DHEA (6 mg/(100 g*d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg*d) daily. The EX group was subcutaneously injected EX 10[mu]g/(kg*d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPK[alpha] and SIRT1 in the ovaries of each group. Results After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 [+ or -] 16.57, 218.63 [+ or -] 13.18 vs 238.30 [+ or -] 12.26 g, P = 0.026), fasting blood glucose (7.71 [+ or -] 0.72, 8.17 [+ or -] 0.54 vs 8.68 [+ or -] 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 [+ or -] 2.50, 7.44 [+ or -] 1.23 vs 12.66 [+ or -] 1.44, P < 0.01) and serum androgen (0.09 [+ or -] 0.03, 0.09 [+ or -] 0.03 vs 0.53 [+ or -] 0.41 ng/ml, P < 0.01) and the expressions of AMPK[alpha] and SIRT11 were increased progressively (P < 0.05). Conclusions Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPK[alpha]-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target. Keywords: Polycystic ovary syndrome, Obesity, Insulin resistance, AMPK[alpha], SIRT1