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Phosphodiesterase 5 inhibitor suppresses prostate weight increase in type 2 diabetic rats

Hisato Kobayashi1, Xinmin Zha1, Keiko Nagase1

  • 1Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.

Life Sciences
|April 3, 2022
PubMed
Abstract

Insights

Phosphodiesterase 5 inhibitors (PDE5i) like tadalafil may prevent prostate enlargement in type 2 diabetes (T2D) by improving blood flow and reducing inflammation. This study investigated PDE5i effects on T2D-related prostate changes.

Area of Science:

  • Endocrinology
  • Urology
  • Diabetology

Background:

  • Hyperinsulinemia is linked to prostate enlargement in type 2 diabetes (T2D), yet clinical observations show growth during hypoinsulinemia.
  • Investigating the mechanisms behind prostate enlargement in T2D and the role of phosphodiesterase 5 inhibitors (PDE5i) is crucial.

Purpose of the Study:

  • To explore the pathogenesis of prostate enlargement in a T2D model (OLETF rats) and its modulation by PDE5i.
  • To assess the impact of tadalafil on prostate weight, blood flow, and molecular markers in T2D and control rats.

Main Methods:

  • Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (T2D model) and Long-Evans Tokushima Otsuka (LETO) rats (control) were treated with tadalafil or vehicle for 12 weeks.
  • Prostate weight, blood flow, and expressions of hypoxia-inducible factor-1 alpha (HIF-1α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), cytokines (IL-6, IL-8, TNF-α), and growth factors (IGF-1, bFGF, TGF-β) were analyzed.

Main Results:

  • OLETF rats exhibited higher prostate weight and lower blood flow compared to LETO rats, with age-related increases.
  • Tadalafil treatment improved prostate blood flow and suppressed prostate weight gain in both rat strains.
  • PDE5i treatment inversely correlated with HIF-1α and 8-OHdG levels and suppressed pro-inflammatory cytokines and growth factors, particularly in T2D rats.

Conclusions:

  • Chronic ischemia in T2D contributes to oxidative stress and prostate enlargement via cytokine and growth factor upregulation.
  • PDE5i treatment demonstrates potential in mitigating prostate ischemia and preventing enlargement in T2D by suppressing key molecular mediators.
Keywords:
CytokineProstateRatTadalafilType 2 diabetes

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