Title: Discovery of microRNA regulatory modules controlling human pancreatic islet function The goal of this research project is to characterize comprehensively the role of microRNAs (miRNAs) in human pancreatic islet function. Islet cells are responsible for the metabolic response to changes in blood glucose levels. Progressive dysfunction of the islet underlies type 2 diabetes, a chronic condition characterized by hyperglycemia, which can lead to substantial morbidity including kidney failure. The gene regulatory networks (GRNs) that drive islet biology are largely uncharacterized. miRNAs are post- transcriptional regulators and critical components of GRNs. Recent studies have implicated miRNAs in islet function. Comprehensive analysis of miRNA expression and activity in primary human islets will significantly increase our knowledge of the GRNs that underlie islet biology. Therefore, this project will use high-throughput genomic approaches to systematically characterize all miRNAs in resting and glucose-stimulated primary human islets (Aim 1), and identify the regulatory modules that influence their differential expression patterns (Aim 2) and targeting activity (Aim 3).
These aims will contribute significantly toward mapping islet GRNs, which will facilitate the identification of clinically relevant pharmacological targets for addressing islet pathophysiology in diabetes.

Public Health Relevance

Type 2 diabetes (T2D) afflicts 285 million people worldwide, is closely associated with the growing obesity epidemic, and leads to substantial morbidity including kidney failure. T2D is characterized by an impaired response to elevated blood glucose levels, which is caused by the progressive dysfunction of the pancreatic islet. The goal of this research project is to characterize comprehensively the role of an important class of biomolecules (microRNAs) in human islet (dys)function, potentially laying a foundation for novel insights into T2D etiology and therapeutics. ) )

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Transition Award (R00)
Project #
5R00DK091318-03
Application #
8475587
Study Section
Special Emphasis Panel (NSS)
Program Officer
Appel, Michael C
Project Start
2012-06-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
3
Fiscal Year
2013
Total Cost
$239,849
Indirect Cost
$62,140
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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