Zinc & ATP: Autocrine Signaling Molecules for Beta Cells

锌

• 批准号: 7157260
• 负责人: CLINTORIA L WILLIAMS
• 金额: $ 2.94万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157260
• 关键词: adenosine triphosphate; autocrine; bioassay; biological signal transduction; cell surface receptors; diabetes mellitus; extracellular; glucose; homeostasis; immunocytochemistry; insulin; laboratory rat; membrane transport proteins; molecular /cellular imaging; pancreatic islets; predoctoral investigator; secretion; stimulus /response; tissue /cell culture; transcription factor; zinc

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：胰腺β细胞的胰岛素分泌对于葡萄糖稳态至关重要。 当胰岛素分泌受损时，当β细胞质量下降或胰岛素抵抗时，糖尿病会导致一种或多种复杂形式。 奇怪的是，缺乏锌也是所有糖尿病状态的标志。 我们假设糖尿病期间β细胞可能会损害锌信号传导和回收利用。 我们假设自分泌细胞外锌和ATP信号传导可能发生在胰岛微环境中，并支持胰腺β细胞稳态。 β细胞和小岛的初步工作支持这些假设。 综上所述，我们提出了一个中心假设，即：锌和ATP由胰腺β细胞分泌，并且具有必不可少的细胞外自分泌作用以及对β细胞稳态和功能的细胞内影响。 我们提出了两个具体目标。 ＃1：针对葡萄糖和其他刺激，定义ATP和锌的分泌或共归因于胰岛素。 ＃2：通过膜受体和转运蛋白检查锌和ATP对β细胞的自分泌支持作用。摘要摘要：其多种形式的糖尿病是由储存血糖激素胰岛素功能的功能丧失引起的。 锌缺乏也与所有形式的糖尿病有关。 寻求支持，保护和/或增强具有锌和/或ATP的胰腺β细胞功能的操作或治疗目标，以了解锌细胞和小岛的锌的细胞保护作用。