IntroductionSexual dysfunction is a common complication in men with type 2 diabetes and is often refractory to treatment. This study investigated the long-term influence of the phosphodiesterase 5 inhibitor (PDE5I) tadalafil on the level of sex hormones and sexual function in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of spontaneous type 2 diabetes.Research design and methodsWe treated 36-week-old male OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats with oral tadalafil (100 µg/kg/day) for 12 weeks; sham groups received vehicle for 12 weeks. Before and after tadalafil treatment, serum levels of total and free testosterone, estradiol, luteinizing hormone (LH), follicle-stimulating hormone and proinflammatory cytokines were compared among four treatment groups. Copulatory function was examined by matching each rat to an estrous female. After completion of the experiment, total fat mass in the abdomen was measured.ResultsTestosterone levels were significantly lower in OLETF versus LETO rats at 36 weeks. After 12 weeks of tadalafil treatment, levels of testosterone were significantly increased both in OLETF-tadalafil and LETO-tadalafil groups versus vehicle groups. Tadalafil decreased estradiol levels both in OLETF and LETO rats. Furthermore, tadalafil increased serum LH levels with a reduction of proinflammatory cytokines. Total fat mass was significantly lower in the OLETF-tadalafil group versus the OLETF-vehicle group. A significant suppression of copulatory behavior, that is, elongation of intromission latency was found in OLETF rats. However, tadalafil treatment for 12 weeks shortened the intromission latency.ConclusionOur results indicate that tadalafil treatment might improve copulatory disorder in the type 2 diabetic model via improvement of an imbalance in sex hormones and an increase in LH levels.

The impact of delivery mode and number of deliveries on urinary incontinence (UI) has been debated, and vaginal delivery has been suggested as a risk factor for female UI. Other potential factors include age, body mass index (BMI), parity, smoking, diabetes mellitus, and hysterectomy. We investigated whether delivery mode and number of deliveries is associated with UI among Japanese women.METHODS: We investigated 514 women recruited from outpatient departments (except the departments of pediatrics, psychiatry and ophthalmology) at our university hospital, regardless of the reason for visiting, during a 2-week period (from August 6 to August 17, 2007). All participants were asked to answer a standardized self-reported questionnaire. Using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), overactive bladder symptom score (OABSS), and an original questionnaire, we evaluated urinary symptoms and delivery mode history.We analyzed the impact of mode and number of deliveries on UI. The chi-square test and logistic regression modeling were used for statistical analyses. Values of P<0.05 were considered statistically significant.RESULTS: A total of 429 individuals completed the questionnaire (response rate, 83.5%). The mean age of respondents was 51.3 years (range, 23-83 years). The prevalence of each disorder was as follows: stress UI (SUI), 38.5%; urgency UI (UUI), 23.5%. The prevalence of UI tended to increase with age. The mean number of deliveries was 2 (range, 0-6). The prevalence of delivery mode was as follows: vaginal, 76%; caesarean (and/or vaginal), 12%; and no deliveries, 12%.Univariate analysis revealed a significant association between number of deliveries and SUI. Age and BMI were also associated with SUI and UUI. In multivariate analysis, the independent risk factors for SUI were age, BMI and number of deliveries (odds ratios (ORs), 1.03, 1.06, and 1.40, respectively). On the other hand, type of delivery was not a risk factor for SUI (Table ). For UUI, only age was identified as an independent risk factor (OR, 1.05; p<0.05).CONCLUSIONS: This study revealed the number of deliveries as an independent risk factor for SUI, but showed no significant relationship between UI and delivery mode among Japanese women.

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133b targeted 3'-UTR of the specificity protein 1 (SP1). ChIP assay demonstrated that SP1 can interact with the GC-rich region in the MYPT1 promoter and CPI-17 gene promoters were governed by the proximal GC-boxes, where SP1 transcription factors bound. Upregulation of miR-133b could down-regulate the expression of SP1, dramatically revert HG-induced phosphorylation level of MYPT1 at The853 of MLCP and CPI-17 at Thr38. In vivo experiment exhibited erectile function in miR-133b agomir group was markedly increased in the diabetic rats compared with the negative control groups and diabetic ED group. Mechanistically, consistented with in vitro experiments, miR-133b supplementation induced relaxation of the CCSM via nitric oxide-independent pathways.CONCLUSIONS: Three miRs were found in diabetic ED rat model. The present results indicate that miR-133b supplementation could improve erectile function in diabetic ED rats probably by regulating the contractility of CCSM via myosin light chain phosphatase inhibition.