Thursday, April 25, 2024 4/25/2024

Insulin Signaling Activates Urothelial Defenses to Reduce Urinary Tract Infection Susceptibility

Award Number: R01DK128088
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Project Summary/Abstract: Diabetes mellitus is associated with many complications, including increased infection risk. With diabetes, one of the most common sites of infection is the urinary tract. In people with diabetes, urinary tract infection (UTI) is more common and has worse outcomes. The mechanisms that predispose people with diabetes to UTI are not defined. A greater appreciation for the host defense mechanisms that protect the urinary tract from microbial insult is needed to develop new UTI prevention and treatment strategies. This application’s objective is to identify how insulin signaling regulates innate immune defenses in the bladder. Our published and supporting data demonstrate that bladder urothelial defenses are regulated by insulin-mediated targets, including peroxisome proliferator-activated receptor-¿ (PPAR¿), insulin receptor signaling, and histone deacetylase proteins. Specifically, our data suggest PPAR¿ activation and histone deacetylase inhibition enhance insulin signaling, strengthen the urothelial barrier, and enhance innate immunity, including the production of antimicrobial peptides and the urothelial barrier. In contrast, silencing urothelial insulin receptor expression increases UTI susceptibility. These data support our central hypothesis that insulin and insulin receptor signaling have key roles in activating innate immune responses and regulating UTI host defense. Expanding upon these findings, we propose a comprehensive analysis of insulin’s ability to regulate bladder urothelial defense mechanisms. Aim 1 will determine the effects of progressive insulin resistance and diabetes on the bladder’s antibacterial defenses. We will also investigate if activating PPAR¿ triggers insulin signaling to enhance immune defenses and reduce UTI susceptibility. Aim 2 will interrogate the impact of insulin receptor signaling on the bladder’s immune defenses and urothelial responses and repair to UTI. Aim 3 will define the effect of histone deacetylase proteins on insulin signaling and the bladder’s immune defenses. Our long-term research goal is to identify why people with diabetes have increased UTI risk and improve their care. By evaluating the role of insulin signaling in host defense, our expected outcomes may have profound influence on human health as they may develop insulin-signaling targets as new UTI therapeutics.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $510,516 )
2023	2023	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	7/26/2023	NON-COMPETING CONTINUATION	$510,516
														Subtotal = $510,516

Issue Date FY: 2022 ( Subtotal = $530,108 )
2022	2022	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	7/28/2022	NON-COMPETING CONTINUATION	$530,108
														Subtotal = $530,108

Issue Date FY: 2021 ( Subtotal = $553,600 )
2021	2021	RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL	700 CHILDRENS DR	COLUMBUS	OH	43205	FRANKLIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/22/2021	NEW	$553,600
														Subtotal = $553,600

Grand Total All Awards = $1,594,224

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Insulin Signaling Activates Urothelial Defenses to Reduce Urinary Tract Infection Susceptibility

Award Number: R01DK128088

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer