Matthew Fraser

Personal Information
Title Associate Professor
Expertise Uropathy
Institution Duke University Medical Center
Data Summary
Grants/SubContracts 1
Progress Reports 1
Presentations 1
Publications 3
Protocols 0
Committees 1
Experiments 0
Strains 0
Models 0


The Effect of Diabetes mellitus on Urethral Neuromuscular Function
Diabetes mellitus (DM) is a debilitating condition characterized by destructive chronic hyperglycemia. Study of the effects of DM on lower urinary tract (LUT) function have been focused on the bladder (diabetic cystopathy). However, the bladder is but one part of the LUT. The urethra serves as the bladder outlet, and must remain closed during storage to maintain continence and must open to provide a low resistance outlet during voiding. Thus, any dysfunction of either closing or opening of the urethra will adversely affect continence or voiding function, respectively, and therefore must be considered when assessing the effects of any disease state on LUT function. Particularly important when considering diabetic cystopathy, a condition characterized by a dilated and hypomotile bladder, is whether the urethra provides a low resistance outlet. While relaxation of the external urethral striated sphincter is passive (due to cessation of its excitation), the opening of the smooth muscle conduit of the urethra is not a passive event, but rather requires active contraction of the urethral longitudinal smooth muscle (mediated by acetylcholine and/or PGE2 ?) and active relaxation of the circular smooth muscle (mediated by nitric oxide). Urethral closure clearly depends on active circular smooth muscle contraction (mediated by norepinephrine at alpha-adrenergic receptors) and may or may not rely on active mechanisms as far as longitudinal smooth muscle relaxation is concerned. In order to understand LUT dysfunction in DM, it is therefore of great importance to investigate what changes in active urethral mechanisms occur (i.e., diabetic urethropathy), what the underlying causative changes might be (e.g., neuropathic or myopathic), and how these changes interact with diabetic cystopathy. In the proposed studies, we will examine longitudinal and circular urethral smooth muscle in both 5, 10 and 20 week vehicle treated or streptozotocin-induced DM rats (in order to track progression of the changes in urethral function). Our experimental strategies will enable us to determine the roles of neuropathy and myopathy in diabetic urethropathy.

Progress Reports

Annual Reports

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Title YearTypeOptions
Fraser, Matthew (2009 P&F)

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