Microfluidic Devices to Determine Roles of Islet-Secreted Leptin

确定胰岛分泌瘦素作用的微流体装置

• 批准号: 7599056
• 负责人: Michael Gabriel Roper
• 金额: $ 28.58万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7599056
• 关键词: Acute; Adipocytes; Adipose tissue; Affect; Area; Automation; Biological; Biological Assay; Biology; Blood Glucose; Cell secretion; Color; Communication; DNA amplification; Development; Diabetes Mellitus; Disease; Glucagon; Glucose; Goals; Health; Human; Hypothalamic structure; Immunoassay; Individual; Insulin; Islets of Langerhans; Knowledge; Lead; Leptin; Measurement; Measures; Methodology; Methods; Microfluidic Microchips; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Pathway interactions; Pattern; Peptides; Peripheral; Physiology; Polymerase Chain Reaction; Protein Secretion; Proteins; Public Health; Research; Research Personnel; Resolution; Role; Route; Satiation; Signal Transduction; Speed; System; Techniques; Technology; Testing; Therapeutic Intervention; Tissues; Work; analytical method; base; biological systems; blood glucose regulation; diabetic; experience; innovation; insulin secretion; insulin sensitivity; islet; islet amyloid polypeptide; new technology; novel; novel therapeutics; pandemic disease; technology development

DESCRIPTION (provided by applicant): Leptin is produced and secreted from islets of Langerhans, but the secretory dynamics and functions of leptin in this setting are unknown. The long-term goal is to quantitatively and simultaneously monitor secretion of peptides and proteins involved in the communication pathway between adipocytes and islets of Langerhans. The overall objective of this application is the development of technology to measure acute changes in leptin secretion from islets of Langerhans and determine how this secretion affects the release of traditional peptides. The central hypothesis is that islet-secreted leptin affects systemic glucose homeostasis by altering islet physiology. To test this hypothesis, the following aims will be accomplished: 1.) acute secretory dynamics of islet-secreted leptin will be determined using an immuno-PCR assay on a microfluidic device, 2.) the effect of leptin on islet physiology will be ascertained by simultaneously monitoring insulin, glucagon, and amylin secretion from islets of Langerhans on a microfluidic device using a multi-color electrophoretic immunoassay, and 3.) the effects that culture conditions have on islet-secreted leptin will be determined using a combination of the technology developed in aims 1 and 2. This work is significant as the role of islet-secreted leptin has not been defined and may identify a new mechanism that influences blood glucose levels. The methodology developed will also be applicable to other biological systems for measurement of simultaneous peptide or protein secretion. The function of islet-secreted leptin has not been investigated, but has the potential to impact broad areas of human health. The proposed research has relevance to public health because this knowledge will increase our understanding of islet biology and potentially provide new routes for alleviating complications associated with diabetes and obesity.

描述（由申请人提供）：瘦素是由朗格汉斯岛产生和分泌的，但瘦素在这种情况下的分泌动力学和功能尚不清楚。长期目标是定量、同时监测参与脂肪细胞和胰岛之间通讯途径的肽和蛋白质的分泌。该应用的总体目标是开发技术来测量朗格汉斯岛瘦素分泌的急剧变化，并确定这种分泌如何影响传统肽的释放。中心假设是胰岛分泌的瘦素通过改变胰岛生理学来影响全身葡萄糖稳态。为了检验这一假设，将实现以下目标：1.) 将使用微流体装置上的免疫 PCR 测定来确定胰岛分泌的瘦素的急性分泌动力学，2.) 将通过使用微流体装置在微流体装置上同时监测胰岛素、胰高血糖素和胰岛淀粉样多肽的分泌来确定瘦素对胰岛生理学的影响。 多色电泳免疫分析，以及 3.) 将结合目标 1 和目标 2 中开发的技术来确定培养条件对胰岛分泌瘦素的影响。这项工作意义重大，因为胰岛分泌瘦素的作用尚未明确，并且可能确定影响血糖水平的新机制。开发的方法也适用于其他生物系统，用于测量同时肽或蛋白质分泌。胰岛分泌的瘦素的功能尚未得到研究，但有可能影响人类健康的广泛领域。拟议的研究与公共卫生相关，因为这些知识将增加我们对胰岛生物学的理解，并可能为减轻与糖尿病和肥胖相关的并发症提供新途径。