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Effect of Diabetes on Prostate Inflammation and Epithelial Hyperplasia
Several studies have demonstrated a positive correlation of BMI with increased prostate size and shown that men diagnosed with symptomatic benign prostatic hyperplasia (BPH) have a higher incidence of diabetes than the general population and that diabetes is associated with more severe symptoms.The mechanism(s) for this association is unclear, although it has been postulated to involve diabetes-associated inflammation and an associated stimulation of prostatic hyperplasia. Even though clinical studies indicate significantly increased risk of BPH and symptomatic progression in men with diabetes, there is a remarkable dearth of laboratory studies on the effect of diabetes on prostate inflammation and growth. Without this knowledge base, it is impossible to speculate on the mechanisms by which diabetes may influence the growth of BPH or the development of lower urinary tract symptomos or to speculate about possible interventions to prevent or reverse these effects. There is, therefore, a compelling need to expand laboratory studies of the prostate in diabetes and to expand prostate research to include studies of prostatic inflammation and neurophysiology in diabetic models. Two specific aims address the hypothesis that diabetes is associated with increased prostatic inflammation and hyperplasia. We will work with the members of the AMDCC to select the appropriate transgenic models and perform the following studies: 1. Test the hypothesis that diabetes is associated with increased prostatic inflammation. A. Use quantitative histologic scoring to compare prostatic inflammation in young adult and older adult diabetic and control mice. B. Use RT-PCR analysis to compare inflammatory mediator expression in young adult and older adult diabetic and control mice. 2. Test the hypothesis that diabetes is associated with epithelial hyperplasia. A. Use quantitative measurements to compare epithelial proliferation in young adult and older adult diabetic and contol mice. B. Use quantitative histologic scoring to compare the incidence of epithelial hyperplasia in young adult and older adult diabetic and contol mice.

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