Ceruloplasmin Mediated Penile Endothelial Dysfunction in Type 1 Diabetes

描述（申请人提供）：糖尿病独特地影响勃起反应的所有组成部分，并且所有共病医学状况赋予ED的最大风险。在对20岁及以上OS男性的基于人群的分析中，所有糖尿病男性中有49%报告了ED。此外，糖尿病男性比无糖尿病男性利用更多的卫生保健资源用于艾德治疗，糖尿病的发病率也在增加。除了糖尿病人群中艾德患病率增加外，该队列中艾德的发病比一般人群早10-15年。这是特别相关的，因为年轻男性更有可能寻求护理和利用医疗保健资源治疗ED。因此，改善或预防男性糖尿病患者艾德的干预措施将变得越来越重要。为了检验我们的一般假设，即糖尿病患者组织特异性阴茎铜蓝蛋白表达增加导致海绵体血管舒张受损和阴茎内皮功能障碍，我们将完成以下具体目标：（1）确定铜蓝蛋白是否通过抑制eNOS活性来抑制NO生物利用度，2）确定铜蓝蛋白在体内对阴茎血管内皮功能的作用，3）研究铜蓝蛋白是否在1型糖尿病小鼠模型中引起阴茎勃起受损。与公共卫生的相关性：治疗或预防男性糖尿病患者的艾德对于提高生活满意度和减少美国人口中这一快速增长部分的卫生保健资源的利用是必要的。 与公共卫生的相关性：治疗或预防男性糖尿病患者的艾德对于提高生活满意度和减少美国人口中这一快速增长部分的卫生保健资源的利用是必要的。

DESCRIPTION (provided by applicant): Diabetes uniquely impacts all components of the erectile response, and all co-morbid medical conditions, imparts the greatest risk of ED. In that population based analysis of OS men aged 20 and up, 49% of all men with diabetes reported ED. Furthermore, men with diabetes utilize more health care resources for ED treatment than men without diabetes, and the incidence of diabetes if increasing. In addition to the increased prevalence of ED in the diabetic population, the onset of ED in this cohort is up to 10-15 years earlier than in the g~neral population. This is particularly relevant because younger men are more likely to seek care and utilize health care resources for the treatment of ED. Thus, interventions to improve or prevent ED in men with diabetes will become increasingly important. To test our general hypothesis that increased tissue specific penile expression of ceruloplasmin in diabetes results in impaired cavernosal vasodilation and penile endothelial dysfunction, we will complete the following specific aims: (1) determine if ceruloplasmin inhibits NO bioavailability through the inhibition of eNOS activity, 2) determine the role of ceruloplasmin on penile vascular endothelial function in vivo, 3) investigate whether ceruloplasmin causes impaired penile erection in a mouse model of type 1 diabetes. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population.