Diabetes mellitus (DM) is a spectrum of debilitating, costly diseases that can lead to multiple and serious complications, as well as premature death. Diabetes and obesity impact the function and structure of all the lower urinary tract (LUT) including bladder, urethral, and prostate;and can lead to complications such as urinary incontinence, poor emptying, and sexual dysfunction. Urologic complications are found in up to 80% of individuals diagnosed with DM, a higher rate than that of widely recognized complications such as neuropathy and nephropathy. The PIs and their teams have extensively studied LUT symptoms of type I DM (T1DM), including characterization of diabetic bladder dysfunction (DBD), prostate growth, and identification of molecular targets at the proteome level in the rodent models. Based on those findings and in response to RFA-DK-10-001, we propose to form the Case Western Reserve University Interdisciplinary Research Center on Urological Complications of Obesity and Diabetes (UCOD). The formation of the Center will: a) formalize our existing interdisciplinary collaboration with established investigators from 6 different research teams;b) expand our work into studies of obesity and type 2 DM;and c) produce high volume preliminary data for future submission of proposals for O'Brien Urology Research Center focusing on UCOD, as one of the most common Benign Urological Diseases affecting our nation. The proposed Center will consist of a research proposal that will function as the scientific road map for our interdisciplinary work on UCOD;an Administrative Core that will plan and implement the short and long term objectives of the Center;and an innovative Enrichment Program that would allow us to share our work on UCOD with 50 other junior and established investigators, post-doctoral (PhD and MD) fellows, and students and provide Institutional support for the work of two Research Scholars who would spend 12 months in our Center. The CWRU Center on UCOD is strongly supported by the CWRU and regional scientific community including the Diabetic Association of Greater Cleveland. This level of support will assure maturation of our Center into a regional Center of Interdisciplinary Research in Benign Urological Disease (IR-BU), the ultimate aim of the RFA-DK-10-001.

Public Health Relevance

Diabetes and obesity, currently on the rise in the U.S., can lead to serious urologic complications. Interdisciplinary studies on the Urologic Complications of Obesity and Diabetes (UCOD) will foster improved and innovative approaches to treatment or prevention of UCOD, which are some of the most common benign urologic diseases affecting our nation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory Grants (P20)
Project #
1P20DK090871-01
Application #
8049850
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (O1))
Program Officer
Hoshizaki, Deborah K
Project Start
2010-09-30
Project End
2012-07-31
Budget Start
2010-09-30
Budget End
2011-07-31
Support Year
1
Fiscal Year
2010
Total Cost
$277,890
Indirect Cost
Name
Case Western Reserve University
Department
Urology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Wu, Liyang; Zhang, Xiaodong; Xiao, Nan et al. (2016) Functional and morphological alterations of the urinary bladder in type 2 diabetic FVB(db/db) mice. J Diabetes Complications 30:778-85
He, Q; Wang, Z; Liu, G et al. (2016) Metabolic syndrome, inflammation and lower urinary tract symptoms: possible translational links. Prostate Cancer Prostatic Dis 19:7-13
He, Qiqi; Babcook, Melissa A; Shukla, Sanjeev et al. (2016) Obesity-initiated metabolic syndrome promotes urinary voiding dysfunction in a mouse model. Prostate 76:964-76
Liu, Guiming; Elrashidy, Rania A; Xiao, Nan et al. (2015) Bladder function in mice with inducible smooth muscle-specific deletion of the manganese superoxide dismutase gene. Am J Physiol Cell Physiol 309:C169-78
Tomechko, Sara E; Liu, Guiming; Tao, Mingfang et al. (2015) Tissue specific dysregulated protein subnetworks in type 2 diabetic bladder urothelium and detrusor muscle. Mol Cell Proteomics 14:635-45
Shankar, Eswar; Vykhovanets, Eugene V; Vykhovanets, Olena V et al. (2012) High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-?B. Prostate 72:233-43
Vykhovanets, Eugene V; MacLennan, Gregory T; Vykhovanets, Olena V et al. (2012) Molecular imaging of nuclear factor-ýýB in bladder as a primary regulator of inflammatory response. J Urol 187:330-7
Daneshgari, Firouz; Brown, Jeanette S; Kusek, John W et al. (2009) Urological complications of obesity and diabetes. J Urol 182:S1