Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway

  • Authors:
    • Yuanyuan Wu
    • Pengfen Li
    • Dan Zhang
    • Yingpu Sun
  • View Affiliations

  • Published online on: December 15, 2017     https://doi.org/10.3892/etm.2017.5650
  • Pages:2120-2127
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Abstract

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5'adenosine monophosphate‑activated protein kinase (AMPK)/phosphoinositide‑3 kinase (PI3K)/c‑Jun N‑terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV‑induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy demonstrated great efficacy in ameliorating PCOS through regulating the AMPK/PI3K/JNK pathway.

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February 2018
Volume 15 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
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APA
Wu, Y., Li, P., Zhang, D., & Sun, Y. (2018). Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway. Experimental and Therapeutic Medicine, 15, 2120-2127. https://doi.org/10.3892/etm.2017.5650
MLA
Wu, Y., Li, P., Zhang, D., Sun, Y."Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway". Experimental and Therapeutic Medicine 15.2 (2018): 2120-2127.
Chicago
Wu, Y., Li, P., Zhang, D., Sun, Y."Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway". Experimental and Therapeutic Medicine 15, no. 2 (2018): 2120-2127. https://doi.org/10.3892/etm.2017.5650