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The Effect of Diabetes mellitus on Urethral Neuromuscular Function
Summary Data Summary
Applicant Fraser, Matthew
E-Mail Address matthew.fraser@duke.edu
Project Title The Effect of Diabetes mellitus on Urethral Neuromuscular Function
CBU ID 09MCG93
External SubContract ID 23789-7
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2009]
Abstract 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.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 36600
Supply Total Costs 9500
Equipment Total Costs 0
Travel/Other Total Costs 8448
Direct Costs 54548
Indirect Costs Proposed 5452
Total Costs Proposed 60000
Total Costs Approved 63000
Start Date 9/30/2009
End Date 8/31/2011
IFO Name Moll, Lorie
IFO E-Mail Address Lorie.Moll@va.gov
IACUC/IRB No. 1425-002
IACUC/IRB Institution VETERANS AFFAIRS MEDICAL CENTER
Entity ID No.
Report Request Date 8/31/2011
T1D NO
TypeCount
Invoices 0
Progress Reports 2
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