AMINO ACID NEUROTRANSMITTERS IN THE ENDOCRINE PANCREAS

内分泌胰腺中的氨基酸神经递质

• 批准号: 2152611
• 负责人: TODD A VERDOORN
• 金额: $ 10万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2152611
• 关键词: GABA receptor; confocal scanning microscopy; glutamate receptor; glycine receptors; hormone regulation /control mechanism; immunofluorescence technique; laboratory mouse; laboratory rat; neurotransmitters; pancreatic islets

THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: (Applicant's abstract) To provide for better understanding of chemical signaling in the pancreatic islets of Langerhans, studies are proposed to examine the functional importance of amino acid neurotransmitters and their receptors in this tissue. Pancreatic islets appear to express receptors for the amino acid neurotransmitters GABA, glycine and glutamate, which subserve rapid synaptic communication between neurons in the central nervous system. The specific goals of the work proposed here are to localize receptor subunit proteins to specific islet cell populations using double immunofluorescence techniques and confocal microscopy. Electrophysiological studies will also be undertaken to determine the role of receptor activation in controlling or modulating the physiological properties of islets. Release of GABA and glutamate from islet cells will be measured in real time. To accomplish this we will use HEK 293 cells expressing recombinant GABA and glutamate receptors as molecular detectors for GABA or glutamate flowing from islets. The effects of receptor activation on insulin and glucagon secretion will be tested through column perifusion studies of isolated islet cells. These studies should improve understanding of how islet cells communicate with each other and with the central nervous system. Numerous disorders are associated with hormonal secretion deficits including type II diabetes, chronic pancreatitis, pancreatic cancer and some neurodegenerative disorders such as Huntington s Disease. This research may provide new insights into the etiology of some forms of Type II diabetes and lead to new treatments for hormone imbalance problems.

这是一个香农奖提供部分支持的研究 项目不属于指定机构的资助范围，但 在优秀的边缘。香农奖旨在提供 支持测试方法的可行性;支持进一步测试 和完善研究技术;进行二次分析或提供 数据集;或进行离散项目，以证明PI 研究能力或为已经优秀的 应用程序.以下摘要摘自原始文件 由主要经销商提交。 描述：（申请人摘要）为了更好地理解 化学信号在胰岛的朗格汉斯，研究 的功能重要性， 神经递质和它们的受体。胰岛 似乎表达氨基酸神经递质GABA的受体， 甘氨酸和谷氨酸，这有助于快速突触通讯 中枢神经系统中的神经元之间。的具体目标 这里提出的工作是将受体亚基蛋白定位到特定的 使用双重免疫荧光技术的胰岛细胞群， 共聚焦显微镜电生理学研究也将 进行了研究，以确定受体激活在控制 或调节胰岛的生理特性。释放GABA 并且来自胰岛细胞的谷氨酸将被真实的实时测量。到 为了实现这一点，我们将使用表达重组GABA的HEK 293细胞， 谷氨酸受体作为GABA或谷氨酸流动的分子检测器 从小岛。受体激活对胰岛素和胰高血糖素的影响 分泌将通过分离的细胞的柱灌注研究进行测试。 胰岛细胞 这些研究应该提高人们对胰岛 细胞之间以及与中枢神经系统之间进行交流。 许多疾病与激素分泌不足有关 包括II型糖尿病、慢性胰腺炎、胰腺癌和 一些神经变性疾病如亨廷顿氏病。这 研究可能会提供新的见解的病因，某些形式的 II型糖尿病并导致激素失衡的新疗法 问题