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DiaComp Funded Abstracts Pilot & Feasibility Funding Programs

Pilot & Feasibility Program Application Abstract
Changes in energy generating pathways as a cause of diabetic bladder dysfunction.
Kelvin Davies   (Bronx, NY)
Diabetes results in several bladder pathologies, a syndrome commonly referred to as diabetic bladder disorder (DBD).There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the development of DBD and generate novel strategies for its treatment. In the preliminary studies presented here we compared the metabolome of detrusor and urothelial layer in a one month streptozotocin (STZ)-induced rat model of Type I diabetes with non-diabetic controls. Diabetes caused several significant changes in the metabolic profile of both tissues potentially related to DBD.However, DBD is a progressive disease in both diabetic patients and animal models and therefore expansion of these studies to consider temporal effects of diabetes on bladder metabolism are warranted. In this proposal we will test the hypothesis that diabetes leads to temporal progressive changes in bladder metabolism which will associate with the development of the pathophysiology of DBD. We will test this hypothesis in two Specific Aims. In Specific Aim 1 we will determine if changes in the bladder metabolome occurs with hyperglycemia, but at a time point prior to the exhibition of bladder pathophysiology. In order to do this we will perform a metabolomics study after one week of Type I diabetes in the STZ-induced rat model and determine if there are changes in the metabolism of the bladder detrusor and urothelium compared to control non-diabetic rats. In Specific Aim 2 we will determine if there are progressive changes in the bladder metabolome caused by diabetes, as the bladder physiology progresses from the compensated to decompensated state. However, when there are changes in the physiology of the bladder, it would be difficult to distinguish which changes in metabolism might be causative of, or a response to, pathophysiology. In an attempt to identify metabolic changes that are a response to the decompensated physiology (rather than due to hyperglycemia), we will look at those changes that occur in the metabolome of the bladder in response to an aged matched non-diabetic decompensated animal model (partial urethral obstruction of the rat). The results from our studies have the potential to give novel insights into the mechanisms leading to the development of DBD and identify novel strategies that could be used to in its prevention and treatment.
No report available yet.