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The effect of high-fat diet on diabetic bladder dysfunction in type 2 diabetes
Summary Data Summary
Applicant Olumi, Aria
E-Mail Address aolumi@bidmc.harvard.edu
Project Title The effect of high-fat diet on diabetic bladder dysfunction in type 2 diabetes
CBU ID 13GHSU245
External SubContract ID 25732-20
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2013]
Abstract Lower urinary tract dysfunction is one of the major but often unrecognized
complications associated with DM2. Patients present with detrusor overactivity
or underactivity. Although diabetic bladder dysfunction affects up to 80% of
patients with DM2, its underlying pathophysiology is poorly understood. We used
a hepatic-specific conditional knockout of insulin receptor substrates 1 & 2
(Irs1, Irs2) genetic mouse model which develops DM2, and demonstrate that the
Irs1/Irs2 double knockout (DKO) mice mimic many of the signs and symptoms seen
in human patients with diabetic lower urinary tract dysfunction. We demonstrate
that the bladders of the DKO mice are overactive (a compensated state of
bladder) in early/mid life of the mice, and underactive (a decompensated state
of bladder) in later adult life. We show that TNF-a, a molecule that is
significantly upregulated in the bladder of diabetic animals, directly
stimulates bladder smooth muscle contraction and activates Rho A signalling.
Systemic inhibition of TNF-a in DKO animals prevents upregulation of Rho A
signaling and reverses the bladder dysfunction. When inhibition of TNF-a is
combined with metformin, bladder dysfunction is improved beyond that achieved
with metformin alone. We hypothesize that TNF-a, a major inflammatory mediator,
is a key effector of diabetic cystopathy. We postulate that obesity, in
combination with DM2 will further increase TNF-a levels, leading to worsening of
bladder dysfunction. In this project, we propose to test this hypothesis in
murine models of DM2.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 39157
Supply Total Costs 18433
Equipment Total Costs 0
Travel/Other Total Costs 1200
Direct Costs 58790
Indirect Costs Proposed 41210
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 10/1/2013
End Date 9/30/2014
IFO Name Horton, Sue
IFO E-Mail Address MGH-G&C@partners.org
IACUC/IRB No. A3596-01
IACUC/IRB Institution Massachusetts General Hospital
Entity ID No. 04-2697983
Report Request Date 10/30/2014
T1D NO
TypeCount
Invoices 10
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  13GHSU24525732-20Massachusetts General Hospital9/10/2014$6,727.47-$6,727.47$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital8/11/2014$7,073.92-$7,073.92$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital7/10/2014$6,029.20-$6,029.20$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital6/10/2014$6,029.20-$6,029.20$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital5/9/2014$6,029.20-$6,029.20$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital4/9/2014$3,465.06$2,564.14$6,029.20$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital3/11/2014$5,435.42$4,022.20$9,457.62$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital2/11/2014$3,465.06$2,564.14$6,029.20$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital11/25/2014$45,045.21-$45,045.21$54.67View PDF
  View  13GHSU24525732-20Massachusetts General Hospital1/10/2014$859.26$635.85$1,495.11$54.67View PDF


Reports
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