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Diabetes Induced Changes in Rat Urinary Bladder and Urethral Epithelium
Diabetic bladder dysfunction (DBD) is among the most common and incapacitating complications of type I diabetes mellitus (DM), resulting in urinary incontinence and poor emptying of the bladder, and affecting quality of life substantially. Despite the prevalence of DBD, many details of the natural history and mechanism of this condition remain unknown. Exploration of those details in a series of laboratory experiments using streptozotocin (STZ)-induced DM in rats has revealed that the bladder undergoes morphometric and functional changes leading to altered voiding function. Recent evidence supports a sensory role for the bladder uro-epithelium and suggests that these epithelial cells may play a prominent role in voiding function in addition to their role as a barrier. Moreover, the role of the urethra has recently been recognized, and alterations in urethral function are also found in DM. Systemically, DM is associated with various changes including plasma osmolarity, glucose levels, and changes in autonomic and neuroendocrine function. These alterations could impact the epithelial cells lining the bladder and urethra and ultimately changes in their sensory function may adversely affect the underlying muscle and innervation. Moreover, changes in epithelial barrier function and urine constituency may be predisposing conditions for infectious/inflammatory processes. In order to begin to explore the effect of DM on epithelial function, we will compare morphological and immunohistochemical characteristics of epithelial cells lining the lower urinary tract (LUT) in normal and STZ-treated DM rats. We hypothesize that the DM-induced epithelial sensory dysfunction will lead to changes in the ‘sensory-web’ directly and thereby result in LUT dysfunction. A secondary effect on bladder function, that caused by altered barrier function necessary during storage, may also be a feature of this disease state. Defects in uro-epithelial sensor molecules and epithelial-signaling (which could lead to activation of bladder afferents) are likely to contribute to the pathogenesis of diabetic bladder dysfunction and impaired sensation. This suggests that targeting urothelial cell sensor molecules and urothelial-cell signaling may lead to novel therapeutic approaches in the treatment of diabetic bladder.

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