Erectile Dysfunction In Diabetes Mellitus Research Articles

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis

Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.

Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis.

Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies. The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM. A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies. A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM. Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.

MP35-07 COMPARISON OF THREE DIFFERENT TADALAFIL REGIMES FOR THE TREATMENT OF ERECTILE DYSFUNCTION IN DIABETES MELLITUS PATIENTS WITH MICROVASCULAR COMPLICATIONS

You have accessJournal of UrologyCME1 May 2022MP35-07 COMPARISON OF THREE DIFFERENT TADALAFIL REGIMES FOR THE TREATMENT OF ERECTILE DYSFUNCTION IN DIABETES MELLITUS PATIENTS WITH MICROVASCULAR COMPLICATIONS Goksel Bayar, and Caglar Yildirim Goksel BayarGoksel Bayar More articles by this author , and Caglar YildirimCaglar Yildirim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002589.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to compare the efficacy and safety of daily, on-demand and daily plus optional tadalafil use in patients with microvascular complications due to diabetes mellitus (DM) and erectile dysfunction (ED). METHODS: Patients who came to our urology outpatient clinic with ED between May 2018 and March 2020, those with at least one microvascular complication due to DM (retinopathy, nephropathy, neuropathy or diabetic foot without macrovascular complications) were selected. Those with an international erectile function index score (IIEF-5) below 11 (severe and moderate) were included in the study. The patients were divided into three groups; the first group 5 mg tadalafil (Cialis™, Lilly, USA) daily, the second group 20 mg tadalafil (Cialis™, Lilly, USA) twice a week two hours before intercourse, and the third group 5 mg tadalafil daily and 2 hours before intercourse twice a week was formed to take an extra 15 mg (20 mg total on the intercourse day) tadalafil. The IIEF-5 form filled with at the first admission. The IIEF-5, SEP-2, SEP-3, GAQ-1 and GAQ-2 inquiry forms were filled 3 months after the treatment. RESULTS: A total of 60 patients, 20 in each group, were included in the study. The mean age, body mass index and baseline IIEF-5 scores of the patients were similar. In the post-treatment IIEF-5 scores, the third group (13+4.7) was significantly higher than the first (8.35+2.6) (p=0.001) and the second group (10+3.6) (p=0.035); there was no significant difference between the first and second groups (p=0.345). Although the percentage of positive answers to SEP-2 and GAQ-1 questions was different between the groups, this difference was not statistically significant. However, the percentage of patients who answered positively to the questions SEP-3 (20%, 40% and 75%, respectively) (p=0.002) and GAQ-2 (20%, 45%, and 75%, respectively) (p=0.002) was significant higher in the third group. There was no difference in the incidence of side effects between the groups (p= 0.392). CONCLUSIONS: Treatment of ED with oral tadalafil in patients with DM-related microvascular complications is ineffective when given daily or before intercourse. In these patients, giving the combination in the first step can provide higher efficacy and patient satisfaction with the same safety. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e589 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Goksel Bayar More articles by this author Caglar Yildirim More articles by this author Expand All Advertisement PDF DownloadLoading ...

Stem cell therapy and diabetic erectile dysfunction: A critical review.

Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

Erectile dysfunction and diabetes: A melting pot of circumstances and treatments.

Diabetes mellitus (DM), a chronic metabolic disease characterised by elevated levels of blood glucose, is among the most common chronic diseases. The incidence and prevalence of DM have been increasing over the years. The complications of DM represent a serious health problem. The long‐term complications include macroangiopathy, microangiopathy and neuropathy as well as sexual dysfunction (SD) in both men and women. Erectile dysfunction (ED) has been considered the most important SD in men with DM. The prevalence of ED is approximately 3.5‐fold higher in men with DM than in those without DM. Common risk factors for the development of DM and its complications include sedentary lifestyle, overweight/obesity and increased caloric consumption. Although lifestyle changes may help improve sexual function, specific treatments are often needed. This study aims to review the definition and prevalence of ED in DM, the impact of DM complications and DM treatment on ED and, finally, the current and emerging therapies for ED in patients with DM.

Serum leptin level in diabetic patients with erectile dysfunction

Background: Erectile dysfunction (ED) is a common sexual problem affecting men. Diabetes mellitus (DM) is one of the most common comorbidities of ED. Leptin is a 167-amino-acid peptide that is mainly expressed in white adipose tissue but is also found in a variety of tissues. Objective: To estimate serum level of leptin in diabetic patients with ED and correlate level of serum leptin in diabetic patients with severity and origin of ED. Patients and methods: Cross-sectional descriptive study was conducted on 64 individual male; 34 diabetic patients of both types of DM with ED and 30 non diabetic normal erectile function as control. All patients were evaluated clinically by history included IIEF-5 score and examination. Assessment of serum leptin level, HbA1c, cholesterol, triglycerides was done and penile duplex study was done only for diseased patients. Results: Serum leptin significantly increased in cases than control (P <0.001). Also, there was increased in diabetic men vasculogenic ED either arterial, venous or mixed (P =0.047). Serum leptin was correlated with the severity of ED (P =0.046). Conclusion: Leptin may play an important biomarker as a cost-effective method for diagnosis and assessment of severity of vasculogenic ED in DM and as a good predictor for ED occurrence.

The Complex Relationship Between Erectile Dysfunction and Hypogonadism in Diabetes Mellitus

As the prevalence of diabetes mellitus grows worldwide, it is increasingly important to understand the commonly comorbid urologic conditions, hypogonadism and erectile dysfunction, in the setting of the diabetic man. The relationship between the diabetes, hypogonadism, and erectile dysfunction is complex with significant interplay among the disease processes and potential for unique management of the triad. The purpose of this review is to provide an update on the intertwined nature of these diseases in diabetics with special consideration for pathophysiology, diagnosis, and management. There is a wide range of pathophysiologic mechanisms central to hypogonadism and erectile dysfunction in diabetes mellitus which continue to be identified and better elucidated; nevertheless, metabolic syndrome, composed of insulin resistance, dyslipidemia, hypertension, and obesity, appears to be the common thread between both. An increasing body of evidence suggests that low testosterone is an independent risk factor for cardiovascular disease and worsened overall survival in diabetic men with potential that testosterone therapy may reduce these risks. The treatment of either erectile dysfunction or hypogonadism in diabetic men may also improve the other condition; some evidence suggests that testosterone therapy in hypogonadal diabetics may improve erectile function while daily vardenafil, in addition to improving erectile function, appears to restore hypogonadal diabetics’ testosterone to the eugonadal range. Metabolic syndrome appears to be the central connection between the increasingly common clinical picture of diabetic men with erectile dysfunction and hypogonadism. The overlapping pathophysiology of these conditions results in unique management considerations.

Association of pupil responses with severity of erectile dysfunction in diabetes mellitus.

Purpose:To investigate the relation between erectile dysfunction (ED) severity and pupillary functions in patients with diabetes mellitus (DM).Methods:This prospective and observational study included 90 patients with type 2 DM and ED. Patients divided into three subgroups according to severity of ED: (i) Mild ED, (ii) Moderate ED and (iii) Severe ED groups. Thirty age-matched healthy subjects formed the control group. Main outcome measures were pupil diameter and average speed of pupil dilation. Static and dynamic pupillometry analysis was performed using the Sirius Topographer (CSO, Firenze, Italy).Results:Mean pupil diameter during static and dynamic pupillometry analysis were significantly greater in the control group than in the all study groups (P < 0.05). Mean pupil diameter in static pupillometry analysis was significantly different in each study group and pupil was more miotic in the Severe ED group than in the both Moderate and Mild ED groups (P < 0.05 for each). Dynamic pupillometry analysis revealed that mean pupil diameter and mean average dilation speed were significantly different in each study group throughout measurement period and the highest speed was observed in the Mild ED group and the lowest speed was observed in the severe ED group (P < 0.005 for each).Conclusion:Our study results suggest that abnormal pupil functions due to diabetic autonomic neuropathy may indicate the associated ED in patients with DM.

Angiotensin II Silencing Alleviates Erectile Dysfunction Through Down-Regulating the Rhoa/Rho Kinase Signaling Pathway in Rats with Diabetes Mellitus

Background/Aims: We aim to explore the role of angiotensin (Ang)II and the RhoA/Rho kinase signaling pathway in the pathogenesis of erectile dysfunction in diabetes mellitus (DM). Methods: Male Sprague-Dawley (SD) rats were used for experiments and short hairpin RNA (shRNA) was used to silence the AngII gene. The erectile function of rats was observed and intracavernous pressure and mean arterial pressure (ICP/MAP) were measured after electrical stimulation. Relaxation and contraction of smooth muscle in the corpus cavernosum were tested. Western blotting and quantitative RT-PCR were applied to measure the expressions of RhoA, Rho-associated kinase (ROCK)1 and ROCK2. Radioimmunoassay was applied to detect the levels of AngII. Results: Rats in the control group had the most erectile times, followed by AngII-silenced rats with DMED and rats with DMED. Rats with DMED had worse ICP and MAP than AngII-silenced rats. The contraction ability was markedly improved and relaxation ability was decreased in AngII-silenced rats with DMED as compared with rats with DMED. The levels of AngII were significantly increased in DMED rats while significantly decreased after AngII silencing. The mRNA and proteins of RhoA and ROCK2 were expressed in a similar way. Conclusion: AngII silencing improves erectile dysfunction via down-regulating the RhoA/Rho kinase signaling pathway.

Serum Biomarkers of Erectile Dysfunction in Diabetes Mellitus: A Systematic Review of Current Literature

Erectile dysfunction (ED) is a common complication in patients with diabetes mellitus (DM). However, the utility of serum biomarkers as clinical surrogates for the development and/or progression of ED is unknown. To summarize the current literature for serum biomarkers for ED in DM and emphasize areas for future research. Human subject data demonstrating the utility of serum markers for the development and progression of ED in patients with DM. We performed a systematic PubMed-Medline search in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using Medical Subject Headings (MeSH) for articles published from January 1, 2000 through December 31, 2016 of serum biomarkers for development or progression of ED in patients with DM using erectile dysfunction [MeSH] AND (biomarkers [MeSH] or inflammation mediators [MeSH] or intercellular signaling peptides and proteins [MeSH] or cell adhesion molecules [MeSH]). A thorough review of these studies was completed. Of the 327 abstracts screened, 12 full-text studies were assessed and 1 study was excluded. Eleven studies assessing serum biomarkers for ED in patients with DM were included in this review. The most studied serum biomarkers for ED in men with DM included endothelial dysfunction markers such as serum E-selectin, endothelial progenitor cells, and endothelial microparticles and specific markers of inflammation such as interleukin-10, ratio of tumor necrosis factor-α to interleukin-10, and reactive oxygen species such as nitric oxide and malondialdehyde. Reliable serum biomarkers will enable earlier diagnosis and objective monitoring of disease progression and responses to treatment in patients with ED. Serum biomarkers for ED in men with DM are very limited. Future longitudinal studies with uniform patient characteristics are needed to evaluate the potential clinical use of serum biomarkers in men with DM for the development and progression of ED. Patel DP, Craig JR, Myers JB, etal. Serum Biomarkers of Erectile Dysfunction in Diabetes Mellitus: A Systematic Review of Current Literature. Sex Med Rev 2017:5:339-348.

The connection of diabetic dyslipidemia and erectile dysfunction

Background Diabetes is an established risk factor for sexual dysfunction in men; a threefold increased risk of erectile dysfunction (ED) was documented in diabetic compared with non-diabetic men. Diabetic vasculopathy concerns macroangiopathy, microangiopathy and endothelial dysfunction. Macrovascular disease in diabetes corresponds to the atherosclerotic damage in the blood vessels, which limits blood flow to the penis. Aim Value the connection of dyslipidemia and erectile dysfunction in men patients who are ill with diabetes. Materials and methods In the research, 180 patients at the age of 33–67 with type 2 diabetes mellitus were participated. According to the duration of diabetes, the patients were divided into three groups and revealed the erectile dysfunction. The lipid metabolism was revealed and HbA1c was determined in all the patients. Results The patients who are ill with diabetes within 1–5 years ( n =41, 22,78%), the erectile dysfunction is met in 34.15% of patients (in this group n =14), those who are ill with diabetes within 5–10 years, the erectile dysfunction is met in 57.53% (in this group n =43), who are ill with diabetes within 10 years and more the erectile dysfunction is met in 69.7% of patients ( n =46). The result of lipid metabolism value showed that hypercholesterolemia was met in 42.22% ( n =76) of the patients, hypertriglyceridemia was met in 21.11% ( n =38), combined disorder was met in 24.44% ( n =44). Thus, 87.77% of the examined patients have lipid metabolism disorder. The result of the research showed that erectile dysfunction was usual in case of dyslipidemia. It should be noted that 60.52% of the patients ( n =23) who had isolated hypertriglyceridemia had erectile dysfunction, 63.16% of the patients ( n =48) who had hypercholesterolemia had erectile dysfunction and 72.73% ( n =32) of the patients with combined disorder had erectile dysfunction. Conclusion Surely, the erectile dysfunction in diabetes mellitus has a multifactorial nature such as duration of diabetes, level of compensation, complications especially neuropathy availability and harmful habits. According to our findings, we have a lot of patients with erectile dysfunction and hypertriglyceridemia. The findings remind us once more that medical practitioners have to pay attention especially to lipid metabolism condition, triglyceridemia level in diabetic patients. So, dyslipidemia is the reason of increasing cardiovascular risks and decreasing quality of life.

Erectile dysfunction in patients with diabetes mellitus: Its magnitude, predictors and their bio-psycho-social interaction: A study from a developing country

BackgroundPersons suffering from diabetes mellitus (DM) are at higher risk of developing erectile dysfunction (ED). Several factors contribute to ED in patients of DM. Only few studies have attempted to explore physical, psychological and social factors in a single study. The aim of the index study was to measure the prevalence of ED in patients of DM and to determine the contributory role of various socio-demographic, physical, and psychological variables. MethodOne hundred and thirteen (N=113) consenting consecutive male married diabetic patients were assessed on International Index of Erectile Function Questionnaire (IIEFQ-5), Dyadic Adjustment Scale (DAS) and Beck's Depression Inventory (BDI) to measure erectile performance, quality of marriage and depressive symptoms respectively. Pretested Bengali versions of these scales were used in the index study. ResultsPrevalence of ED was 38.94%. ED group significantly differed from non-ED group in current age, family type, type of treatment for diabetes, presence of micro/macrovascular complications, history of current tobacco use, quality of marriage, and presence of depressive symptoms. In logistic regression analysis current age, body mass index (BMI) and presence of depressive symptoms had significant predictive role on occurrence of erectile dysfunction. ConclusionPrevalence of ED among diabetic patients is high compared to general population. Both physical and psychosocial factors predict the occurrence of ED in this group. So, both physicians and psychiatrists should remain aware about the multi-faceted causative role of ED in DM.

Role of angiotensin II and angiotensin-(1–7) in diabetes-induced oxidative DNA damage in the corpus cavernosum

To investigate diabetes mellitus (DM)-induced oxidative DNA damage, putative involvement of angiotensin (Ang) II, and possible modulatory effects of Ang-(1-7) in rat corpus cavernosum (CC). In vivo study. Research laboratory. Adult male Wistar rats. Streptozotocin-induced diabetic rats received either captopril, losartan (both 300 mg/L in drinking water), or Ang-(1-7) (576 μg/kg/d IP) for a 3-week period immediately before sacrifice at 6 weeks of DM. Histopathological changes in CC were examined in Masson's trichrome-stained tissue sections. Oxidative stress was evaluated by measuring total oxidant status and antioxidant status. The DNA damage was estimated by measuring 8-hydroxy-2'-deoxyguanosine by immunohistochemistry and ELISA. The CC smooth muscle degeneration was observed in association with an increase in total oxidant status and a decrease in total antioxidant status in rats with DM. Oxidative DNA damage was significantly increased in both cytoplasm and nuclei of CC in DM. Treatment with captopril, losartan, or Ang-(1-7) inhibited these changes in rats with DM. The data indicate that Ang II signaling is involved in DM-induced structural changes and oxidative DNA damage in the CC and that modulation of the signaling by captopril, losartan, and Ang-(1-7) restores the effects of DM. Thus, Ang-(1-7)/MAS1 axis may be a novel therapeutic target for erectile dysfunction in DM.

Exercise Training Improves the Defective Centrally Mediated Erectile Responses in Rats with Type I Diabetes

Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for the penile erection. The goal of the present study was to determine the impact of exercise training (ExT) on the centrally mediated erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats. Male Sprague-Dawley rats were injected with STZ to induce diabetes mellitus. Three weeks after STZ or vehicle injections, rats were assigned to either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four experimental groups: control + sedentary, T1D + sedentary, control + ExT, and T1D + ExT. After 3-4 weeks ExT, central N-methyl-D-aspartic acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular nucleus (PVN) of the hypothalamus was measured by using histochemistry, real time polymerase chain reaction (PCR) and Western blot approaches. In rats with T1D, ExT significantly improved the blunted erectile response, and the intracavernous pressure changes to NMDA (50 ng) microinjection within the PVN (T1D + ExT: 3.0 ± 0.6 penile erection/rat; T1D + sedentary: 0.5 ± 0.3 penile erection/rat within 20 minutes, P < 0.05). ExT improved erectile dysfunction induced by central administration of exogenous nitric oxide (NO) donor, SNP in T1D rats. Other behavior responses including yawning and stretching, induced by central NMDA and SNP microinjection were also significantly increased in T1D rats after ExT. Furthermore, we found that ExT restored the nNOS mRNA and protein expression in the PVN in T1D rats. These results suggest that ExT may have beneficial effects on the erectile dysfunction in diabetes through improvement of NO bioavailability within the PVN. Thus, ExT may be used as therapeutic modality to up-regulate nNOS within the PVN and improve the central component of the erectile dysfunction in diabetes mellitus.

Edaravone Ameliorates Diabetes-Induced Dysfunction of NO-Induced Relaxation in Corpus Cavernosum Smooth Muscle in the Rat

Diabetes mellitus (DM) represents a major risk factor for erectile dysfunction (ED). Although the etiology of diabetes-induced ED is multifactorial and still unknown, reactive oxygen species are thought to be one of the key factors. The aim of this article is to investigate whether administration of edaravone, a free radical scavenger, could prevent type 1 diabetes-induced dysfunction of nitric oxide (NO)-induced relaxation in corpus cavernosum smooth muscle in the rat. Six-week-old male Wistar rats were randomly divided into three groups. One group was treated with citrate-phosphate buffer plus normal saline (group Cont), whereas in the other two groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally [i.p.]). Subsequently, the diabetic rats were treated for 4 weeks either with edaravone (10 mg/kg/day, i.p.; group DM + E) or with normal saline (group DM). Serum glucose and malondialdehyde levels as well as penile cyclic guanosine monophosphate (cGMP) concentrations were determined, and penile function was estimated by organ bath studies with norepinephrine-mediated contractions and acetylcholine-mediated relaxations. The participation mRNA levels of muscarinic M(3) receptors, neuronal nitrous oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), and participation protein levels of nNOS, eNOS, phosphorylated nNOS, and phosphorylated eNOS were investigated by quantitative real-time polymerase chain reaction (PCR) and immunoblot analysis, respectively. Treatment with edaravone prevented partially but significantly the decreased body and penile weight induced by diabetes. Treatment with edaravone significantly improved the increased diabetes-induced malondialdehyde levels, the decreased penile cGMP concentrations, the increased diabetes-induced norepinephrine-mediated contractions, and the decreased acetylcholine-mediated relaxation. Although there were no significant differences in expression levels of mRNAs in nNOS, diabetes-induced upregulation of muscarinic M(3) receptor and iNOS mRNAs as well as diabetes-induced downregulations of eNOS, phosphorylated nNOS, and phosphorylated eNOS were significantly prevented by edaravone. Edaravone decreases the oxidative insult in the penile corpus cavernosum by ameliorating the NO-NOS system and thus preventing partially the developing ED in DM in the rat.

Erectile dysfunction in diabetes mellitus contributes to poor quality of life

Erectile dysfunction (ED) is seen in a large number of male patients with diabetes mellitus (DM). However, little is known about the impact of ED on quality of life (QoL) of DM patients. To study the QoL of men with type 2 diabetes mellitus (T2DM) and ED and compare the same for men with DM without ED 63 patients of DM with ED were compared with 30 matched patients (on sociodemographic and clinical profile, rating on depression and anxiety) of DM without ED on QoL measures using WHO-QoL-Bref. Patients with ED had poorer QoL in all domains (except the physical domain); however, the differences between the two groups were significant only for the environmental domain. ED contributes to poorer QoL in patients with diabetes mellitus.

Sodium ferulate treatment and interventional mechanism reverse erectile dysfunction in streptozotocin-induced diabetic rats

To investigate the effect and mechanism of sodium ferulate (SF) on reversing erectile dysfunction in diabetes mellitus (DM) rats. Forty-four male adult Sprague-Dawley rats were induced for diabetes by an intraperitoneal injection of streptozotocin. Then the successful models were randomly divided into DM + SF group and DM group (22 rats each respectively). The rats in DM +SF group were treated with sodium ferulate (100 mg x kg(-1) x d(-1)) through a daily gastric lavage. At Week 12, the erectile function of all rats was evaluated and serum samples were harvested. The SOD, CAT, NOS, MDA and NO levels in corpus cavernosum and serum were all measured. The pathologic change in penile cavernous body was observed microscopically. The diabetic rat models were successfully established. The erectile function was much better in normal control group and DM + SF group than that in DM group. And the penile erection rates in three groups were 100%, 66% and 22% respectively. The activity levels of SOD, CAT and NOS were markedly decreased in DM group as compared to those in normal control group and DM + SF group (P < 0.01). The NO content was approximately equal in normal control group and DM + SF group (112 +/- 28) nmol/ml vs (137 +/- 25) nmol/ml. But both were much higher than that in DM group (56 +/- 10) nmol/ml, both P < 0.01. The MDA content was markedly increased in DM group as compared to those in normal control group and DM + SF group (both P < 0.01). Microscopically, muscle fibers in penile cavernous body arranged disorderly, muscular mantle damaged and desmoplasia scattered among muscle fibers in DM group. Sodium ferulate may play interventional roles in reversing diabetic erectile dysfunction through metabolic regulation of free radicals, antagonism of oxidative insults and enhancement of NO production.

Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis

Erectile dysfunction (ED) is a major complication of diabetes mellitus (DM). This study investigates the relationship between ED and the downregulation of constitutive nitric oxide synthase (cNOS) in the corpus cavernosum (CC) of diabetic rats. It also examines the effects of udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on ED and cNOS expression levels. After 16 weeks of daily oral treatment with udenafil in diabetic rats, the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio was recorded to measure erectile function, and cNOS expression was measured using reverse transcriptase (RT)-PCR and immunoblots. Although the ICP/MAP ratio and the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in the CC were markedly decreased in diabetic rats, long-term udenafil treatment improved the erectile function and increased cNOS expression compared with diabetic controls. These findings suggest that ED in DM is closely related to decreased cNOS expression in the CC and that udenafil has the ability to compensate for this pathological change by modulating cNOS expression. Udenafil also has an inhibitory role in cGMP (cyclic guanosine monophosphate) degradation.

Erectile dysfunction in diabetes mellitus: a risk factor for cardiovascular disease

Erectile dysfunction in diabetes mellitus: a risk factor for cardiovascular disease

Localization of Increased Insulin-Like Growth Factor Binding Protein-3 in Diabetic Rat Penis: Implications for Erectile Dysfunction

Diabetes-induced erectile dysfunction (ED) is assumed to result from neurovascular abnormalities. However, the entire picture of the molecular mechanisms underlying ED has not yet been clarified. To elucidate the possible elements involved in ED in diabetes mellitus, we performed broad-scale gene expression profiling using cDNA array in the penis of streptozotocin-induced diabetic rats. Northern blot analysis was performed to examine the course of the mRNA expression encoded by the identified gene. Immunohistochemistry was performed to identify the cellular localization of the encoded protein. Of the genes investigated, the expression level of insulin-like growth factor binding protein 3 (IGFBP-3) was greatly increased at 12 weeks after streptozotocin treatment. The levels of ErbB3 epidermal growth factor receptor-related proto-oncogene, G1/S-specific cyclin D2, hepatic neutral cholesteryl ester hydrolase precursor, UDP-galactose ceramide galactosyltransferase, and serine protease RNK-Met-1 were markedly decreased. Increased levels of IGFBP-3 mRNA were demonstrated as early as 2 weeks after induction of hyperglycemia. Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was first observed in the penis of the 8-week diabetic rats, and a significant reduction in the intracavernous pressure was demonstrated only at 12 weeks after the induction of hyperglycemia. These results suggest that the increased expression of IGFBP-3 during hyperglycemia might play an important role in the development of ED.