Skip to main content

Advertisement

Log in

Effects of metformin on prostatic tissue of rats with metabolic syndrome and benign prostatic hyperplasia

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Objectives

To investigate the efficacy of insulin sensitizer on prostatic tissue in animal model with benign prostatic hyperplasia (BPH) secondary to metabolic syndrome (MetS).

Methods

Models were established by providing Sprague–Dawley rats with high fat diet (HFD) combined with metformin or not. All objects were killed 40 days later with prostatic tissue being removed, weighed before stained, as well as the expression level of insulin-like growth factor I (IGF-1) and receptor (IGF-1R) being measured, and the level of insulin resistance (IR) has also been evaluated.

Results

Model has been successfully established. Level of prostatic hyperplasia and IR as well as IGF-1 and IGF-1R expressions in the blank and saline control subunits of HFD group was higher than that of normal diet group (P < 0.05). In the subunit of metformin, along with the suppression of IR, the level of prostatic hyperplasia and the expression of IGF-1 pathway have both decreased (P < 0.05).

Conclusion

MetS can promote the growth of prostate during the formation of central obesity and IR. IGF-1 pathway may have an important role in the induction of BPH following IR. The application of metformin can suppress the expression of IGF-1 and IGF-1R, thus preventing the promotive effect of IR on prostate tissue in animal model of MetS.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Parsons JK (2010) Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr Bladder Dysfunct Rep 5(4):212–218

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kasturi S, Russell S, McVary KT (2006) Metabolic syndrome and lower urinary tract symptoms secondary to benign prostatic hyperplasia. Curr Urol Rep 7(4):288–292

    Article  PubMed  Google Scholar 

  3. Vignozzi L, Gacci M, Maggi M (2016) Lower urinary tract symptoms, benign prostatic hyperplasia and metabolic syndrome. Nat Rev Urol 13(2):108–119

    Article  CAS  PubMed  Google Scholar 

  4. Antunes LC, Elkfury JL, Jornada MN, Foletto KC, Bertoluci MC (2016) Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Arch Endocrinol Metab 60(2):138–142

    Article  PubMed  Google Scholar 

  5. Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, Tubaro A, Oelke M, Carini M, Maggi M (2015) Metabolic syndrome and benign prostatic enlargement: a systematic review and meta- analysis. BJU Int 115(1):24–31

    Article  PubMed  Google Scholar 

  6. Gacci M, Sebastianelli A, Salvi M, De Nunzio C, Tubaro A, Vignozzi L, Corona G, McVary KT, Kaplan SA, Maggi M, Carini M, Serni S (2015) Central obesity is predictive of persistent storage LUTS after surgery for benign prostatic enlargement: results of a multicenter prospective study. BJU Int 116(2):271–277

    Article  PubMed  Google Scholar 

  7. Lee RK, Chung D, Chughtai B, Te AE, Kaplan SA (2012) Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms. BJU Int 110(4):540–545

    Article  PubMed  Google Scholar 

  8. Russo GI, Castelli T, Privitera S, Fragalà E, Favilla V, Reale G, Urzì D, La Vignera S, Condorelli RA, Calogero AE, Cimino S, Morgia G (2015) Increase of Framingham cardiovascular disease risk score is associated with severity of lower urinary tract symptoms. BJU Int 116(5):791–796

    Article  PubMed  Google Scholar 

  9. De Nunzio C, Aronson W, Freedland SJ, Giovannucci E, Parsons JK (2012) The correlation between metabolic syndrome and prostatic diseases. Eur Urol 61(3):560–570

    Article  PubMed  Google Scholar 

  10. Minutoli L, Altavilla D, Marini H, Rinaldi M, Irrera N, Pizzino G, Bitto A, Arena S, Cimino S, Squadrito F, Russo GI, Morgia G (2014) Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene. J Biomed Sci 21:19

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kassi E, Pervanidou P, Kaltsas G, Chrousos G (2011) Metabolic syndrome: definitions and controversies. BMC Med 9:48

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zou C, Gong D, Fang N, Fan Y (2016) Meta-analysis of metabolic syndrome and benign prostatic hyperplasia in Chinese patients. World J Urol 34(2):281–289

    Article  CAS  PubMed  Google Scholar 

  13. De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, Sciarra A, Tubaro A (2011) The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol 60(1):106–117

    Article  PubMed  Google Scholar 

  14. Wang Z, Olumi AF (2011) Diabetes, growth hormone-insulin-like growth factor pathways and association to benign prostatic hyperplasia. Differentiation 82(4–5):261–271

    Article  CAS  PubMed  Google Scholar 

  15. Gacci M, Vignozzi L, Sebastianelli A, Salvi M, Giannessi C, De Nunzio C, Tubaro A, Corona G, Rastrelli G, Santi R, Nesi G, Serni S, Carini M, Maggi M (2013) Metabolic syndrome and lower urinary tract symptoms: the role of inflammation. Prostate Cancer Prostatic Dis 16(1):101–116

    Article  CAS  PubMed  Google Scholar 

  16. Neuhouser ML, Schenk J, Song YJ, Tangen CM, Goodman PJ, Pollak M, Penson DF, Thompson IM, Kristal AR (2008) Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. Prostate 68(13):1477–1486

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rohrmann S, Giovannucci E, Smit E, Platz EA (2007) Association of IGF-1 and IGFBP-3 with lower urinary tract symptoms in the third national health and nutrition examination survey. Prostate 67(15):1693–1698

    Article  CAS  PubMed  Google Scholar 

  18. Luo J, Dunn T, Ewing C, Sauvageot J, Chen Y, Trent J, Isaacs W (2002) Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate 51(3):189–200

    Article  CAS  PubMed  Google Scholar 

  19. Fiorelli G, De Bellis A, Longo A, Giannini S, Natali A, Costantini A, Vannelli GB, Serio M (1991) Insulin-like growth factor-I receptors in human hyperplastic prostate tissue: characterization, tissue localization, and their modulation by chronic treatment with a gonadotropin-releasing hormone analog. J Clin Endocrinol Metab 72(4):740–746

    Article  CAS  PubMed  Google Scholar 

  20. Monti S, Di Silverio F, Iraci R, Martini C, Lanzara S, Falasca P, Poggi M, Stigliano A, Sciarra F, Toscano V (2001) Regional ariations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type I in benign prostatic hyperplasia tissue and their correlation with intraprostatic androgens. J Clin Endocrinol Metab 86(4):1700–1706

    CAS  PubMed  Google Scholar 

  21. Li W, Wu CL, Febbo PG, Olumi AF (2007) Stromally expressed c-Jun regulates proliferation of prostate epithelial cells. Am J Pathol 171(4):1189–1198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ruan W, Powell-Braxton L, Kopchick JJ, Kleinberg DL (1999) Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development. Endocrinology 140(5):1984–1989

    Article  CAS  PubMed  Google Scholar 

  23. Kaplan SA, Lee JY, O’Neill EA, Meehan AG, Kusek JW (2013) Prevalence of low testosterone and its relationship to body mass index in older men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Aging Male 16(4):169–172

    Article  CAS  PubMed  Google Scholar 

  24. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25

    Article  CAS  PubMed  Google Scholar 

  25. Colquhoun AJ et al (2012) Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis 15:346–352

    Article  CAS  PubMed  Google Scholar 

  26. Ruiter R et al (2012) Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care 35(1):119–124

    Article  CAS  PubMed  Google Scholar 

  27. Murtola TJ et al (2008) Antidiabetic medication and prostate cancer risk: a population-based case-control study. Am J Epidemiol 168(8):925–931

    Article  PubMed  Google Scholar 

  28. He XX, Tu SM, Lee MH et al (2011) Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol 22(12):2640–2645

    Article  PubMed  PubMed Central  Google Scholar 

  29. Margel D et al (2013) Metformin use and all-cause and prostate cancer- specific mortality among men with diabetes. J Clin Oncol 31(25):3069–3075

    Article  CAS  PubMed  Google Scholar 

  30. Wright JL, Stanford JL (2009) Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control 20(9):1617–1622

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kusturica J, Kulo Ćesić A, Gušić E, Maleškić S, Rakanović-Todić M, Šečić D (2017) Metformin use associated with lower risk of cancer in patients with diabetes mellitus type 2. Med Glas (Zenica) 14(2):176–181

    Google Scholar 

  32. Zhang Y, Li MX, Wang H, Zeng Z, Li XM (2015) Metformin down-regulates endometrial carcinoma cell secretion of IGF-1 and expression of IGF-1R. Asian Pac J Cancer Prev 16(1):221–225

    Article  PubMed  Google Scholar 

  33. Wang Z, Xiao X, Ge R, Li J, Johnson CW, Rassoulian C, Olumi AF (2017) Metformin inhibits the proliferation of benign prostatic epithelial cells. PLoS ONE 12(3):e0173335

    Article  PubMed  PubMed Central  Google Scholar 

  34. Mosli HH, Esmat A, Atawia RT, Shoieb SM, Mosli HA, Abdel-Naim AB (2015) Metformin attenuates testosterone-induced prostatic hyperplasia in rats: a pharmacological perspective. Sci Rep 23(5):15639

    Article  Google Scholar 

Download references

Acknowledgements

Relevant personnel from the department of pathology, laboratory animal center, and urology of Anhui provincial hospital have provided a great deal of help.

Funding

This study was funded by Natural Science Foundation of Anhui Province (1408085QH152).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tao Huang.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethics committee

The use of animal in this research was approved by the ethics committee of experimental animal of Anhui medical university.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, C., Xu, Y., Shen, Z. et al. Effects of metformin on prostatic tissue of rats with metabolic syndrome and benign prostatic hyperplasia. Int Urol Nephrol 50, 611–617 (2018). https://doi.org/10.1007/s11255-018-1826-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-018-1826-9

Keywords

Navigation