Effects of metformin and Exenatide on insulin resistance and AMPK\u03b1-SIRT1 molecular pathway in PCOS rats

Xin Tao,Shuqi Ge,Lisi Cai,Xuanying Deng,Lei Chen

doi:10.1186/s13048-019-0555-8

Abstract

AimsThis study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms.MethodsAn 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 10μg/(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 AMPKα and SIRT1 in the ovaries of each group.ResultsAfter 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05).ConclusionsBoth metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.

Highlights

The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age with a prevalence of 5–10% [1]
PCOS, a syndrome of unknown etiology, is associated with accumulation of abdominal fat, obesity (BMI > 30 kg/m2) and insulin resistance (IR), which are present in 70–80% of women of PCOS [2]
The PCOS group rats were subcutaneously injected for 20 days with dehydroepiandrosterone (DHEA 6 mg/(100 gd)) (Millipore (252805)) and 0.2 ml injectable soybean oil; while the Normal control (NC) group rats were subcutaneously injected with only 0.2 ml of injectable soybean oil

Summary

Introduction

The polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age with a prevalence of 5–10% [1]. The syndrome is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovaries. PCOS, a syndrome of unknown etiology, is associated with accumulation of abdominal fat, obesity (BMI > 30 kg/m2) and insulin resistance (IR), which are present in 70–80% of women of PCOS [2]. There is increasing global data linking PCOS to metabolic complications, such as impaired glucose tolerance (IGT), type 2 diabetes (DM2), dyslipidemia, Insulin sensitizers, especially metformin (MF), have been shown as a pharmaceutical option aiming at IR, and several other aspects of PCOS, including reproductive dysfunctions [4]. A lot of studies have confirmed the protective impact of MF on IR and

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Conclusion