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Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome

  • Authors:
    • Fan Wang
    • Shaobing Wang
    • Zhenghong Zhang
    • Qingqiang Lin
    • Yiping Liu
    • Yijun Xiao
    • Kaizhuan Xiao
    • Zhengchao Wang
  • View Affiliations / Copyright

    Affiliations: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China, State Key Laboratory for Evaluation of Exercise Physiological Functions from General Administration of Sport of China, School of Physical Education and Sport Sciences, Fujian Normal University, Fuzhou, Fujian 350007, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8164-8170
    |
    Published online on: September 29, 2017
       https://doi.org/10.3892/mmr.2017.7678
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Abstract

It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear. The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS. In the present study, a PCOS rat model was induced by letrozole, and successful establishment of the model was confirmed by examining ovarian histology and determining serum testosterone levels, by hematoxylin and eosin staining and ELISA, respectively. Subsequently, the expression of two key elements of insulin signaling, insulin receptor substrate (IRS)‑2 and phosphatidylinositol 3‑kinase (PI3K), was determined by immunohistochemistry and western blot analysis. The results demonstrated that IRS‑2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment. These results indicate that IRS‑2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS. To further confirm the effects of DMBG on insulin signaling expression during this process, the expression of an additional two downstream proteins, phosphoinositide‑dependent kinase‑1 (PDK‑1) and the mammalian target of rapamycin (mTOR), was also investigated in the present study, and the results demonstrated that the expression of PDK‑1 and mTOR was significantly reduced in PCOS ovaries and increased following DMBG treatment, further indicating that altered insulin signaling may have an important role in the development and treatment of PCOS. In conclusion, the results of the present study indicate that the reduced expression of proteins involved in insulin signaling may contribute to the development of the clinical features of PCOS, and DMBG reverses reduced expression of insulin signaling components, by a mechanism that is yet to be determined, to attenuate certain symptoms of PCOS, such as obesity. To the best of our knowledge, the present study is the first to provide data regarding the detailed changes of insulin signaling during the development and treatment of PCOS, and may provide an important reference for clinical PCOS treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Wang F, Wang S, Zhang Z, Lin Q, Liu Y, Xiao Y, Xiao K and Wang Z: Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. Mol Med Rep 16: 8164-8170, 2017.
APA
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y. ... Wang, Z. (2017). Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. Molecular Medicine Reports, 16, 8164-8170. https://doi.org/10.3892/mmr.2017.7678
MLA
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y., Xiao, K., Wang, Z."Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome". Molecular Medicine Reports 16.6 (2017): 8164-8170.
Chicago
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y., Xiao, K., Wang, Z."Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome". Molecular Medicine Reports 16, no. 6 (2017): 8164-8170. https://doi.org/10.3892/mmr.2017.7678
Copy and paste a formatted citation
x
Spandidos Publications style
Wang F, Wang S, Zhang Z, Lin Q, Liu Y, Xiao Y, Xiao K and Wang Z: Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. Mol Med Rep 16: 8164-8170, 2017.
APA
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y. ... Wang, Z. (2017). Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome. Molecular Medicine Reports, 16, 8164-8170. https://doi.org/10.3892/mmr.2017.7678
MLA
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y., Xiao, K., Wang, Z."Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome". Molecular Medicine Reports 16.6 (2017): 8164-8170.
Chicago
Wang, F., Wang, S., Zhang, Z., Lin, Q., Liu, Y., Xiao, Y., Xiao, K., Wang, Z."Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome". Molecular Medicine Reports 16, no. 6 (2017): 8164-8170. https://doi.org/10.3892/mmr.2017.7678
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