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Targeting mitochondria to prevent obesity induced bladder dysfunction
Summary Data Summary
Applicant Hannan, Johanna
E-Mail Address hannanj14@ecu.edu
Project Title Targeting mitochondria to prevent obesity induced bladder dysfunction
CBU ID 17AU3837
External SubContract ID 32307-13
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2017]
Abstract One of the most common and debilitating complications of obesity is diabetic
bladder dysfunction which significantly impacts the quality of life of diabetic
patients and has a large medical financial burden. The pathophysiology of
bladder dysfunction during type 2 diabetes mellitus (T2DM) impacts the
urothelium, smooth muscle and/or the autonomic nerves. T2DM bladder dysfunction
is associated with increased inflammation, hypoxia and neurovascular dysfunction
all of which may affect tissue function. However, at this time no pathological
mechanism has been identified that can explain completely the onset of diabetic
bladder dysfunction, thus hindering the development of an effective treatment.
Our preliminary experiments demonstrated that mice chronically fed a high fat
diet (HFD, 45% kcal from fat) had increased diuresis and electrical field
stimulated (EFS) mediated contraction, which was associated with impaired
mitochondrial respiration and increased hydrogen peroxide (H2O2) production
potential in the detrusor. Based on the results of our preliminary experiments,
our objective is to focus on the energetics of the mitochondria as a primary
driver of bladder dysfunction during HFD-induced T2DM. We propose to test the
novel hypothesis that the development of bladder dysfunction is the result
increased mitochondrial respiration and increased ROS emission in the bladder
tissue. To meet our objective, we have developed a novel approach for assessing
respiratory function of the bladder, in which we can determine O2 respiration
with minimal disruption to the anatomical structure of the bladder or native
biochemical arrangement of the mitochondria. We will examine our hypothesis with
the following 2 aims. In Aim 1, we will evaluate the contribution of reduced
mitochondrial respiration in the urothelium and detrusor smooth muscle from mice
fed a short or chronic HFD to alterations in bladder function. In Aim 2, we will
determine the ability of mitochondrial catalase overexpression to prevent
HFD-induced bladder dysfunction. A multidisciplinary team science approach has
been used in this proposal to study the role of bladder mitochondrial function
in obesity-induced T2DM symptoms of urinary incontinence. We anticipate that
these studies will help elucidate the mechanism of bladder dysfunction that
occurs during HFD-induced type 2 diabetes.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Spangenburg, Espen E.; Fraser, Matthew O.; Neufer, P. Darrell; Pak, Elena
Salary Total Costs 35789
Supply Total Costs 19303
Equipment Total Costs 0
Travel/Other Total Costs 12535
Direct Costs 67627
Indirect Costs Proposed 32123
Total Costs Proposed 99750
Total Costs Approved 99750
Start Date 11/1/2017
End Date 5/31/2019
IFO Name Friedrich, Jeff
IFO E-Mail Address friedrichj14@ecu.edu
IACUC/IRB No. Q347
IACUC/IRB Institution East Carolina University Brody School of Medicine
Entity ID No.
Report Request Date 6/30/2019
T1D NO
TypeCount
Invoices 13
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  17AU383732307-13East Carolina University Brody School of Medicine9/12/2019$418.18$198.64$616.82$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine8/17/2018$953.90$453.11$1,407.01$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine7/25/2019$21,563.91$10,242.93$31,806.84$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine7/12/2018$1,456.56$691.87$2,148.43$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine6/21/2018$525.82$249.76$775.58$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine5/15/2019$6,284.44$2,985.08$9,269.52$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine5/10/2018$846.40$402.04$1,248.44$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine4/12/2019$4,491.77$2,133.59$6,625.36$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine3/7/2019$5,903.94$2,804.38$8,708.32$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine2/14/2019$6,437.80$3,057.92$9,495.72$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine12/10/2018$12,547.54$5,960.04$18,507.58$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine11/25/2019---$8,801.41View PDF
  View  17AU383732307-13East Carolina University Brody School of Medicine10/15/2018$1,880.23$893.12$2,773.35$8,801.41View PDF


Reports
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