MP89-19 ALTERED CAVEOLIN EXPRESSION IN DIABETIC PENIS: POSSIBLE ROLE IN ERECTILE DYSFUNCTION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology II1 Apr 2016MP89-19 ALTERED CAVEOLIN EXPRESSION IN DIABETIC PENIS: POSSIBLE ROLE IN ERECTILE DYSFUNCTION M. Raj Rajasekaran, Johnny Fu, Adam Kassan, Alice Zemljic-Harpf, Valmik Bhargava, Karnam S Murthy, and Hemal Patel M. Raj RajasekaranM. Raj Rajasekaran More articles by this author , Johnny FuJohnny Fu More articles by this author , Adam KassanAdam Kassan More articles by this author , Alice Zemljic-HarpfAlice Zemljic-Harpf More articles by this author , Valmik BhargavaValmik Bhargava More articles by this author , Karnam S MurthyKarnam S Murthy More articles by this author , and Hemal PatelHemal Patel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2480AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pathophysiology of increased severity of erectile dysfunction (ED) in diabetic men and their poor response to phosphodiesterase 5 (PDE5) inhibitors are unclear. A defective vascular endothelium and consequent impairment in formation and/or action of nitric oxide (NO) are implicated as possible causes. Endothelial NO synthase (eNOS) is localized to caveolae (plasma membrane lipid rafts). Caveolins (Cav), structural components of caveolae, are recognized to play a regulatory role in the vascular complications of diabetes. Our objectives are to: (i) evaluate changes in Cav-1 and Cav-3 expression in penile tissue of type 2 diabetes (T2DM) mice and (ii) measure impact of Cav-1 deletion on penile PDE5 activity. METHODS We used wild type C57BL6, Cav-1 and Cav-3 KO male mice (n=6 each). To create T2DM mouse model, C57BL6 (15-18 months) male mice were injected with a single dose streptozotocin (non-fasted, 75 mg/kg i.p.) and switched to high fat diet (HFD; 60% kcal of total calories). Two months after HFD, serum glucose and GTT (glucose tolerance test) were performed to confirm metabolic disorder. Animals were maintained on HFD for 4 months and euthanized to harvest penile tissues. Expression levels of Cav-1 and Cav-3 were determined by Western blot and PDE5 activity was measured using [3H]cGMP as the substrate. RESULTS A significant increase in body weight and impairment in GTT were observed in HFD-fed mice (Fig 1). A significant decrease in both Cav-1 and Cav-3 levels were observed in T2DM mice (D1-3) compared to WT mice (C1-2; Fig 2A). Stimulation of PDE5 activity in response to NO donor, GSNO was significantly higher (~2 fold) in Cav1- KO (Fig 2B) compared to WT mice. CONCLUSIONS Altered penile Cav-1 levels in T2DM mice and increased PDE5 activity after Cav-1 depletion suggests a regulatory role for Cav-1 in diabetes related ED. Targeting caveolins may be a novel approach to improve pharmacotherapeutic response in T2DM patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1144 Advertisement Copyright & Permissions© 2016MetricsAuthor Information M. Raj Rajasekaran More articles by this author Johnny Fu More articles by this author Adam Kassan More articles by this author Alice Zemljic-Harpf More articles by this author Valmik Bhargava More articles by this author Karnam S Murthy More articles by this author Hemal Patel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...