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

基本信息

批准号：
8037744
负责人：
Michael Gabriel Roper
金额：
$ 27.84万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
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/8037744
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

项目摘要

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）：瘦素是从Langerhans的胰岛产生和分泌的，但是在这种情况下，瘦素的分泌动力和功能是未知的。长期的目标是定量，同时监测与langerhans脂肪细胞和胰岛之间通信途径有关的肽和蛋白质的分泌。该应用的总体目的是开发技术来衡量兰格汉斯胰岛瘦素分泌的急性变化，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会影响系统性葡萄糖稳态。 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多色电泳免疫测定法和3.）培养条件对胰岛分泌的瘦素的影响将使用AIMS 1和2中开发的技术的组合确定。这项工作很重要，因为胰岛分泌的瘦素的作用尚未定义，并且可能识别出影响血糖水平的新机制。开发的方法也将适用于其他生物系统，用于测量同时的肽或蛋白质分泌。尚未研究胰岛分泌的瘦素的功能，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有关，因为这些知识将增加我们对胰岛生物学的理解，并有可能为减轻与糖尿病和肥胖相关的并发症提供新的途径。