Increased Phosphodiesterase Type 5 Levels in a Mouse Model of Type 2 Diabetes Mellitus

Ellati, Riyad T.; Dokun, Ayotunde O.; Kavoussi, Parviz K.; Steers, William D.; Annex, Brian H.; Lysiak, Jeffrey J.

doi:10.1111/j.1743-6109.2012.02854.x

Cited by 10 publications

(11 citation statements)

References 45 publications

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“…Briefly, diabetic microangiopathy causes atherosclerosis and thrombosis, which leads to the narrowing of the artery lumen, subsequently reducing bloodflow to the penis. In addition, microangiopathy is involved in ED through affecting autonomic neuropathies (23)(24)(25)(26)(27). In the present study, the results demonstrated that the incidence of DR and DN was significantly higher in the ED group compared with the NED group (P<0.05), which indicated that diabetic patients with ED suffered from severe microangiopathy.…”

Section: Discussionsupporting

confidence: 62%

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction

Jiang¹,

Luo²,

Zhao³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the expression of microRNA (miR)-93, miR-320 and miR-16 and to assess their diagnostic value in diabetic patients with erectile dysfunction (ED). A total of 120 individuals were divided into three groups, which included the diabetics with ED group (ED group), the diabetics without ED group (NED group) and the healthy volunteers group (control group). Each group included 40 individuals. Serum samples were collected and reverse transcription quantitative polymerase chain reaction detection of the three types of miRNA was performed and the sensitivity of ED was analyzed by receiver operating characteristic curves. A negative correlation was identified between the incidence of ED in patients with diabetes and serum total testosterone levels (r=0.302, P<0.05); however, a positive correlation was observed between the incidence of ED in diabetics and the HbA1c level (r=0.231, P<0.05). Additionally, the relative expression levels of the three types of miRNA were higher in the ED group when compared with the NED and control groups (P<0.05). When compared with the control group, the area under the curve (AUC) values for miR-93, miR-320 and miR-16 were 0.793, 0.818 and 0.810, respectively, in the ED group and 0.576, 0.532 and 0.542 in the NED group, respectively. Furthermore, when compared with the NED group, the AUC value for miR-93, miR-320 and miR-16 was 0.707, 0.810 and 0.833, respectively, in the ED group. Therefore, the expression levels of miR-93, miR-320 and miR-16 may be useful for the early diagnosis of ED in patients with diabetes.

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Section: Discussionsupporting

confidence: 62%

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction

Jiang¹,

Luo²,

Zhao³

et al. 2015

Experimental and Therapeutic Medicine

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“…Mice were fed freely and maintained on a 12‐hour dark–light cycle. Our laboratory has previously reported that mice fed with a diet consisting of 60% fat will develop ED compared with mice on normal chow diet [12,15]. C57Bl/6J mice were put onto a 60% HFD (Jackson Laboratories, Bar Harbor, ME, USA) at 6 weeks of age and remained on the HFD for 22 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Intracorporal pressures (ICPs) were obtained before and during cavernosal nerve electrical stimulation (CNES) in both HFD‐fed and control mice (n = 7 per group). Baseline ICPs and CNES ICPs were performed as previously described [15]. Briefly, under anesthesia, the cavernous nerves were exposed.…”

Section: Methodsmentioning

confidence: 99%

Alterations in microRNA Expression in a Murine Model of Diet-Induced Vasculogenic Erectile Dysfunction

Barbery

Celigoj

Turner

et al. 2015

The Journal of Sexual Medicine

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Introduction MicroRNAs (miRs) are noncoding, endogenous RNA molecules that regulate gene expression and play roles in response to vascular injury. Aim The aim of this study was to identify miRs expressed in corporal tissue (CT) and to determine whether miRs demonstrate differential expression in a mouse model of diet-induced erectile dysfunction (ED). Methods RNA was isolated from the CT from control mice and mice with diet-induced ED. A quantifiable miR profiling technique (NanoString) was used to determine the expression of over 600 miRs. Main Outcome Measures Differential expression analysis was performed using a negative binomial regression model for count-based data. Mean expression levels, fold change, and false discovery-corrected P values were determined. Candidate miRs were validated via quantitative polymerase chain reaction (Q-PCR). Results In control mice, NanoString analysis revealed that 181 miRs were expressed above background levels and 5 miRs were expressed at high levels. Diet-induced ED resulted in the up-regulation of 6 miRs and the down-regulation of 65 miRs in the CT compared with mice on control diet. Focusing on the upregulated miRs, we chose five for Q-PCR validation. Of these five, two (miR-151-5p and miR-1937c) demonstrated significance via Q-PCR, whereas the other three (miR-720, miR-1937a, miR-205) trended in the correct direction. Conclusions MiRs may play a significant role in mRNA regulation in CT and specific miRs may be involved in diet-induced vasculogenic ED. Future studies are aimed at determining the mRNA targets of these miRs.

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“…Basic scientific studies indicate that increased oxidative stress and reduced nitric oxide (NO) bioavailability are the major derangements underlying the development and progression of vasculogenic and neurogenic ED associated with DM (Long et al, 2012; Vernet et al, 1995; Luttrell et al, 2008; Carneiro et al, 2010; Elliati et al, 2013; Albersen et al, 2011; Chiou et al, 2010; Oger et al, 2014; Kataoka et al 2014; Musicki et al, 2016; Xie et al, 2007; Kovanecz et al, 2009; Chitaley 2009; Nunes et al, 2015; Wingard et al, 2007; Sanchez et al, 2012). In diabetic patients ED is similarly related to reduced NOS activity, as evidenced by elevated arginase activity (Bivalacqua et al, 2001) and decreased nNOS protein expression (Dashwood et al, 2011), nitrate/nitrite (Tuncayengin et al, 2003) and cGMP content (Angulo et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

Musicki¹,

Burnett²

2017

Andrology

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Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis surgery for ED, and from 6 control patients without T2DM or ED who underwent penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by Western blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and nitrotyrosine-modified proteins were significantly (p<0.05) increased compared to control values. Total eNOS and nNOS protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2DM-associated ED in the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2DM-associated ED at the human level is relevant for advancing clinically therapeutic approaches to restore erectile function in T2DM patients.

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Increased Phosphodiesterase Type 5 Levels in a Mouse Model of Type 2 Diabetes Mellitus

Cited by 10 publications

References 45 publications

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction

Clinical significance and expression of microRNA in diabetic patients with erectile dysfunction

Alterations in microRNA Expression in a Murine Model of Diet-Induced Vasculogenic Erectile Dysfunction

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

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