Journal article
Increased Phosphodiesterase Type 5 Levels in a Mouse Model of Type 2 Diabetes Mellitus
Journal of sexual medicine, Vol.10(2), pp.362-369
02/2013
DOI: 10.1111/j.1743-6109.2012.02854.x
PMID: 22812665
Abstract
Diabetes mellitus (DM) is a major risk factor for developing erectile dysfunction (ED) and men with DM are often less responsive to phosphodiesterase type 5 (PDE5) inhibitors than ED due to other causes.
The aim of this study was to explore potential mechanisms whereby PDE5 inhibitors may have reduced efficacy in type 2 DM.
At 4 weeks of age, mice were either fed a high‐fat diet (HFD) for 22–36 weeks or fed regular chow (control). An additional group of mice in the same genetic background had a genetic form of type 1 DM.
Glucose tolerance testing, intracorporal pressures (ICPs), oxidative stress (OS), apoptotic cell death (active caspase‐3 and apostain), PDE5, p53, and cyclic guanosine monophosphate (cGMP) levels, and histological examination of inflow arteries were performed in mice fed a HFD and control mice. A group of mice with type 1 DM were studied for PDE5 expression levels.
All mice fed a HFD had impaired glucose tolerance compared with the age‐matched mice fed on standard chow diet (control). HFD fed mice had reduced maximum ICPs following in vivo cavernous nerve electrical stimulation and increased apoptotic cell death, OS, and p53 levels in the corporal tissue. Interestingly, PDE5 levels were increased and cGMP levels were decreased. In contrast, mice with type 1 DM did not have increases in PDE5.
Taken together, our results suggest that type 2 DM‐induced ED is associated with findings that could lead to reduced cGMP and may account for reduced efficacy of PDE5 inhibitors. Ellati RT, Dokun AO, Kavoussi PK, Steers WD, Annex BH, and Lysiak JJ. Increased phosphodiesterase type 5 levels in a mouse model of type 2 diabetes mellitus. J Sex Med **;**:**–**.
Details
- Title: Subtitle
- Increased Phosphodiesterase Type 5 Levels in a Mouse Model of Type 2 Diabetes Mellitus
- Creators
- Riyad T. Ellati - Department of Urology, University of VirginiaAyotunde O. Dokun - University of Virginia Health SystemParviz K. Kavoussi - Department of Urology, University of VirginiaWilliam D. Steers - Department of Urology, University of VirginiaBrian H. Annex - University of Virginia Health SystemJeffrey J. Lysiak - Department of Urology, University of Virginia
- Resource Type
- Journal article
- Publication Details
- Journal of sexual medicine, Vol.10(2), pp.362-369
- Publisher
- Elsevier Inc
- DOI
- 10.1111/j.1743-6109.2012.02854.x
- PMID
- 22812665
- ISSN
- 1743-6095
- eISSN
- 1743-6109
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984297608902771
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