Urinary bladder hypertrophy in experimental diabetes mellitus

2型糖尿病（T2DM）是21世纪全球最大的健康挑战之一。尽管80%的糖尿病患者存在排尿功能障碍，但与糖尿病的心血管或神经系统并发症相比，排尿功能障碍受到的关注要少得多。在最常用的糖尿病动物模型，注射链脲佐菌素的大鼠中，膀胱肥大一直被观察到，但这是1型糖尿病的模型。关于2型糖尿病患者膀胱肥大的数据很少且相互矛盾，尽管雌性动物同样经常受到糖尿病的影响，但在已发表的文献中，雌性动物的代表性严重不足。现有的膀胱肥大的治疗和预防数据仅限于胰岛素，并且没有用于T2DM的典型口服治疗的数据。在此背景下，我们提出了未来研究的五个主要目标：1。探讨膀胱肥大在更广泛的糖尿病模型，特别是2型糖尿病和女性。2. 测试胰岛素以外的治疗预防和/或逆转膀胱肥大的能力。3. 描述两性糖尿病大鼠模型平滑肌反应性的变化，包括口服抗糖尿病和抗肥厚药物治疗。4. 探讨T1DM和T2DM模型膀胱平滑肌代谢组的变化，包括两性及口服降糖和抗肥厚药物治疗。5. 探讨膀胱肥大和纤维化的分子和细胞机制，包括两性和口服抗糖尿病和抗肥大药物的治疗。整个方案本质上是探索性的，旨在为后续项目的设计提供必要的信息，包括模型选择，并进行深入的机制调查。该项目的德国部分有两名来自美因茨和柏林的申请人；第三名调查员驻扎在安卡拉（土耳其）。这项申请只要求资助德国调查人员；另一份具有相同科学内容的申请已提交给TÜBITAK，为土耳其研究人员提供资金，同时也已获得批准。

Type 2 diabetes (T2DM) is one of the biggest global health challenges of the 21st century. Despite occurring in 80% of diabetic patients, voiding dysfunction has received much less attention than cardiovascular or neurological complications of diabetes. Hypertrophy of the urinary bladder is consistently observed in the most frequently used animal model of diabetes, the streptozotocin-injected rat, but this is a model of type 1 diabetes. Data on bladder hypertrophy in T2DM are sparse and contradictory and female animals are heavily underrepresented in the published literature despite being similarly often affected by diabetes. Existing treatment and prevention data on bladder hypertrophy are restricted to insulin, and no data are available on oral treatments typically used in T2DM. Against this background, we propose five main objectives for our future research: 1. Explore bladder hypertrophy in a larger variety of diabetes models, particularly of T2DM and in females. 2. Test ability of treatments other than insulin to prevent and/or reverse bladder hypertrophy. 3. Characterize changes in smooth muscle reactivity in diabetic rat models of both sexes and including treatment with oral antidiabetic and anti-hypertrophic drugs. 4. Explore changes of the metabolome in smooth muscle of the bladder of T1DM and T2DM models, including both sexes and treatment with oral antidiabetic and anti-hypertrophic drugs. 5. Explore molecular and cellular mechanisms of hypertrophy and fibrosis of the bladder, including both sexes and treatment with oral antidiabetic and anti-hypertrophic drugs. The overall program is exploratory in nature and designed to generate the necessary information, including model selection, for the design of a subsequent project with in-depth mechanistic investigation. The German part of the project hast wo applicants from Mainz and Berlin; a third investigator is based in Ankara (Turkey). This application only requests funding for the German investigators; a separate application of identical scientific content has been submitted to TÜBITAK for funding for the Turkish investigators, and has meanwhile been approved.