Urinary bladder hypertrophy in experimental diabetes mellitus

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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.