Urinary bladder hypertrophy in experimental diabetes mellitus

2型糖尿病(T2 DM)是21世纪最大的全球健康挑战之一。尽管80%的糖尿病患者会发生排尿功能障碍，但与糖尿病的心血管或神经并发症相比，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，膀胱肥大的现象一直存在，但这是一种1型糖尿病模型。关于T2 DM患者膀胱肥大的数据稀少且相互矛盾，尽管雌性动物同样经常受到糖尿病的影响，但在已出版的文献中，雌性动物的比例严重不足。现有的关于膀胱肥大的治疗和预防数据仅限于胰岛素，而没有关于通常用于T2 DM的口服治疗的数据。在此背景下，我们提出了未来研究的五个主要目标：1.探索更多类型的糖尿病模型中的膀胱肥大，特别是T2 DM和女性。2.测试胰岛素以外的其他治疗方法预防和/或逆转膀胱肥大的能力。3.研究糖尿病大鼠模型的血管反应性变化，包括口服抗糖尿病药物和抗肥厚药物。4.探讨T1 DM和T2 DM模型中不同性别及口服降糖、抗肥厚药物治疗后膀胱平滑肌代谢组的变化。5.探讨膀胱肥大和纤维化的分子和细胞机制，包括性别和口服抗糖尿病和抗肥大药物治疗。整个计划是探索性的，旨在生成必要的信息，包括型号选择，以用于后续项目的设计和深入的机械调查。该项目的德国部分有来自美因茨和柏林的两名申请者；第三名调查员设在安卡拉(土耳其)。这项申请只要求为德国调查人员提供资金；另一份具有相同科学内容的申请已提交给TÜBITAK，要求为土耳其调查人员提供资金，并已同时获得批准。

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.