Skip to main content
SpringerLink
Log in

Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To evaluate the effect of electro-acupuncture (EA) in infertile patients with phlegm-dampness polycystic ovary syndrome-insulin resistance (PCOS-IR).

Methods

Seventy-six PCOS-IR patients who underwnet in vitro fertilization and embryo transfer (IVF-ET) were equally assigned to two groups according to a random digital table: the EA group and the control group, with 38 cases in each group. Before undergoing IVF, the two groups were treated with EA or pseudo-acupuncture, respectively, for 3 menstrual cycles. The intervention was 25 min twice a week until the day of oocyte collection. The selected acupoints were Zhongwan (RN 12), Tianshu (ST 25), Daheng (SP 15), Daimai (GB 26), Qihai (CV 6), Guanyuan (CV 4), and bilateral points including Xuehai (SP 10), Fenglong (ST 40), Zusanli (ST 36), and Yinlingquan (SP 9). Evaluation of phlegm-dampness syndrome score and IR score were carried out before and after treatment. Additionally, the number of oocytes retrieved, transplantable embryo rate, high-quality embryo rate, clinical pregnancy rate and live birth rate were compared between the two groups. Real-time polymerase chain reaction analysis was used to monitor the mRNA expression of the insulin receptor substrate (IRS-1), phosphatidylinositiol 3-kinase (PI3K) and glucose transport factor 4 (GLUT4) in ovarian granulosa cells.

Results

EA treatment reduced the phlegm-dampness syndrome score as well as the IR scores compared with the control group (P<0.05). No significant differences in the number of oocytes retrieved and clinical pregnancy rate between the two groups (P>0.05). Moreover, the transplantable embryo rate [49.0% (284/580) vs. 41.9% (273/652)], high-quality embryo rate [36.6% (104/284) vs. 27.8% (76/273)], and live birth rate [50% (19/38) vs. 26.3% (10/38)] in the EA group were significantly higher than in the control group (P<0.05). Gene expression analyses revealed significantly elevated IRS-1, PI3K and GLUT4 mRNA in ovarian granulosa cells of the EA group compared with the control group (P<0.05).

Conclusions

EA may ameliorate the effects of phlegm-dampness syndrome and ovarian IR in PCOS-IR patients. Mechanistically, this effect might be through an upregulation of the IRS-1/PI3K/GLUT4 signaling pathway, which may result in improved oocyte quality and embryonic development potential. (Registration No. ChiCTR1800015453).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Livadas S, Diamanti-Kandarakis E. Polycystic ovary syndrome: definitions, phenotypes and diagnostic approach. Front Horm Res 2013;40:1–21.

    CAS  PubMed  Google Scholar 

  2. Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol 2010;122:42–52.

    Article  CAS  Google Scholar 

  3. Jin J, Ruan X, Hua L, Tian X, Li Y, Wang L, et al. Prevalence of diminished ovarian reserve in Chinese women with polycystic ovary syndrome and sensitive diagnostic parameters. Gynecol Endocrinol 2017;33:694–697.

    Article  Google Scholar 

  4. Cassar S, Misso ML, Hopkins WG, Shaw CS, Teede HJ, Stepto NK. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum Reprod 2016;31:2619–2631.

    Article  CAS  Google Scholar 

  5. Zeng XQ, Zhang CM, Tong ML, Chi X, Li XL, Ji CB, et al. Knockdown of NYGGF4 increases glucose transport in C2C12 mice skeletal myocytes by activation IRS-1/PI3K/AKT insulin pathway. J Bioenerg Biomembr 2012;44:351–355.

    Article  CAS  Google Scholar 

  6. Kim E, Seok HH, Lee SY, Lee DR, Moon J, Yoon TK, et al. Correlation between expression of glucose transporters in granulosa cells and oocyte quality in women with polycystic ovary syndrome. Endocrinol Metab (Seoul) 2014;29:40–47.

    Article  Google Scholar 

  7. Li J, Cui W, Sun W, Zhang QY, Guan Q. Effect of electroacupuncture on the spindle and oocytes quality in patients with PCOS. Chin J Integr Tradit West Med (Chin) 2015;35:304–309.

    Google Scholar 

  8. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41–47.

  9. Jeanes YM, Reeves S. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges. Nutr Res Rev 2017;30:97–105.

    Article  Google Scholar 

  10. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.

  11. Medical Administration Department of State Administration of Traditional Chinese Medicine Clinical Path of TCM for 105 Diseases in 24 Specialties (Trial Implementation). Beijing: Beijing State Administration of Traditional Chinese Medicine; 2011:522–523.

    Google Scholar 

  12. Macpherson H, White A, Cummings M, Jobst K, Rose K, Niemtzow R. Standards for reporting interventions in controlled trials of acupuncture: the STRICTA recommendations. Complement Ther Med 2001;9:246–249.

    Article  CAS  Google Scholar 

  13. Moher D, Schulz KF, Altman DG. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. J Am Podiatr Med Assoc 2001;91:437–442.

    Article  CAS  Google Scholar 

  14. Wu HC, Zhang JW, Sun ZG, Xiang S, Qiao Y, Lian F. Effects of electroacupuncture on expression of PI3K/Akt/Foxo3a in granulosa cells from women with Shen (Kidney) deficiency syndrome undergoing in vitro fertilization-embryo transfer. Chin J Integr Med 2019;25:252–258.

    Article  CAS  Google Scholar 

  15. Zheng XY, ed. Guidelines for clinical research of new Chinese herbs for treatment of irregular menstruation, amenorrhea and infertility. Beijing: China Medical Science and Technology Press; 2002:388–390.

    Google Scholar 

  16. Sakkas D, Gardner DK, Weissman A, eds. Textbook of reproductive techniques: laboratory perspectives. 4th ed. London: Informa Health Press;2012:240–53.

    Google Scholar 

  17. Thorens B, Mueckler M. Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab 2010;298:E141–E145.

    Article  CAS  Google Scholar 

  18. Carvajal R, Rosas C, Kohan K, Gabler F, Vantman D, Romero C, et al. Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients. Hum Reprod 2013;28:2235–2244.

    Article  CAS  Google Scholar 

  19. Ezeh U, Chen IY, Chen YH, Azziz R. Adipocyte expression of glucose transporter 1 and 4 in PCOS: relationship to insulin-mediated and non-insulin-mediated whole-body glucose uptake. Clin Endocrinol (Oxf) 2019;90:542–552.

    Article  CAS  Google Scholar 

  20. Johansson J, Feng Y, Shao R, Lonn M, Billig H, Stener-Victorin E. Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome. Am J Physiol Endocrinol Metab 2010;299:E551–E559.

    Article  CAS  Google Scholar 

  21. Gonzalez-Munoz E, Lopez-Iglesias C, Calvo M, Palacin M, Zorzano A, Camps M. Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degradation in 3T3-L1 adipocytes. Endocrinology 2009;150:3493–3502.

    Article  CAS  Google Scholar 

  22. Pagliassotti MJ, Kang J, Thresher JS, Sung C K, Bizeau ME. Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance. Am J Physiol Endocrinol Metab 2002;282:E170–E176.

    Article  CAS  Google Scholar 

  23. Pauli JM, Raja-Khan N, Wu X, Legro RS. Current perspectives of insulin resistance and polycystic ovary syndrome. Diabet Med 2011;28:1445–1454.

    Article  CAS  Google Scholar 

  24. Archuleta TL, Lemieux AM, Saengsirisuwan V, Teachey MK, Lindborg KA, Kim JS, et al. Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: role of p38 MAPK. Free Radic Biol Med 2009;47:1486–1493.

    Article  CAS  Google Scholar 

  25. Zhang HY, Zhang YF, Han YK, Xue FX, Zhao XH, Zhang XL. Activation and significance of the PI3K/Akt pathway in endometrium with polycystic ovary syndrome patients. Chin J Obstetr Gynecol (Chin) 2012;47:19–23.

    CAS  Google Scholar 

  26. Behboudi-Gandevani S, Ramezani TF, Rostami DM, Farahmand M, Bahri KM, Noroozzadeh M, et al. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies. Gynecol Endocrinol 2016;32:343–353.

    Article  CAS  Google Scholar 

  27. Zhao X, Peng H, Yue WX, Li HY, Chen Q. To demonstrate the relationship between obesity and insulin resistance from phlegm dampness. World Latest Med Inf (Chin) 2019;19:90–91.

    Google Scholar 

  28. Kou LH, Hou LH, Wang Y, Meng XY. Clinical characteristics of polycystic ovary syndrome differentiated as Spleen deficiency and phlegm damp. Word J Integr Tradit West Med (Chin) 2017;12:598–600, 621.

    Google Scholar 

Download references

Acknowledgments

We thank all the participants in this study for their involvement.

Author information

Authors and Affiliations

  1. Gynecology of Traditional Chinese Medicine, the First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

    Shan Xiang, Jing-yan Song & Dan-qi Liu

  2. Reproductive and Genetic Center of Integrated Traditional and Western Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China

    Shan Xiang, Jing-yan Song & Fang Lian

  3. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China

    Ming-feng Xia

Authors
  1. Shan Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-feng Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing-yan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan-qi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fang Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xiang S collected patient information, collected ovarian granulosa cells and wrote the manuscript. Xia MF, Song JY, Liu DQ administrated the project. Lian F investigated the research and critically revised the manuscript.

Corresponding author

Correspondence to Fang Lian.

Additional information

Conflict of Interest

The authors who have participated in this study declare that they have no conflicts of interest.

Supported by the Shandong Natural Science Foundation (No. ZR2019QH013), Shandong Natural Science Foundation (No. 2018CXGC130), State Administration of Foreign Experts Affairs, China (No. P192023031)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiang, S., Xia, Mf., Song, Jy. et al. Effect of Electro-acupuncture on Expression of IRS-1/PI3K/GLUT4 Pathway in Ovarian Granulosa Cells of Infertile Patients with Polycystic Ovary Syndrome-Insulin Resistance of Phlegm-Dampness Syndrome. Chin. J. Integr. Med. 27, 330–335 (2021). https://doi.org/10.1007/s11655-020-3219-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-020-3219-z

Keywords

Search

Navigation