Insulin secretion from pancreatic beta-cells is critical for glucose homeostasis. When insulin secretion is impaired, when beta-cell mass declines or when resistance to insulin occurs, diabetes results in one or more complex forms. Curiously, zinc deficiency is also a hallmark of all diabetic states. We hypothesize that zinc signaling and recycling may be impaired in beta-cells during diabetes. We postulate that autocrine extracellular zinc and ATP signaling may occur within islet microenvironments and support pancreatic beta-cell homeostasis. Preliminary work in beta-cells and islets supports these hypotheses. Taken together, we pose the central hypothesis that: Zinc and ATP are secreted by pancreatic beta-cells and have essential extracellular autocrine influence and intracellular effects on beta-cell homeostasis and function. We propose two specific aims. #1: Define the secretion or co-secretion of ATP and zinc with insulin in response to glucose and other stimuli. #2: Examine autocrine supportive effects of zinc and ATP for beta-cells via membrane receptors and transporters. Lay Summary: Diabetes in its multiple forms is caused by loss of function of the blood glucose-storing hormone, insulin. Zinc deficiency has also been linked to all forms of diabetes. Maneuvers or therapeutic targets that support, protect and/or augment pancreatic beta-cell function with zinc and/or ATP are sought to understand cytoprotective roles of zinc for beta-cells and islet. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM078758-02
Application #
7289741
Study Section
Minority Programs Review Committee (MPRC)
Program Officer
Gaillard, Shawn R
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2007
Total Cost
$29,382
Indirect Cost
Name
University of Alabama Birmingham
Department
Physiology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294