Nonstationary Isotopic Tracer Analysis of Hepatocytes

肝细胞的非稳态同位素示踪分析

• 批准号: 7159345
• 负责人: Jamey D. Young
• 金额: $ 4.45万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159345
• 关键词: analytical method; computer program /software; computer system design /evaluation; diabetes mellitus; laboratory mouse; liver cells; liver metabolism; postdoctoral investigator; stable isotope; technology /technique development

DESCRIPTION (provided by applicant): There are three specific aims of the project, which are to (a) develop a methodology for metabolic flux estimation based on nonstationary isotopic tracer experiments, (b) create a general-purpose software application for analysis and interpretation of nonstationary isotopic tracer experiments, and (c) to apply the aforementioned theoretical results and software tools to analyze hepatocyte metabolism under diabetic and normal conditions. This research will provide a deeper understanding of the mechanisms by which the liver responds to diabetic disease states, thus leading to novel strategies for disease treatment, monitoring, and diagnosis. By allowing tracer studies to be performed during the transient period preceding isotopic steadystate, the techniques developed in this project will permit flux estimates to be obtained within a shorter timeframe than traditional methods. Because the liver-specific functions of hepatocytes often degrade over time, it is important to analyze these cells soon after they are isolated from the liver to get an accurate picture of the in vivo flux state.

描述（申请人提供）：该项目有三个具体目标，即（a）开发一种基于非稳态同位素示踪实验的代谢通量估算方法，（B）创建一个用于分析和解释非稳态同位素示踪实验的通用软件应用程序，以及（c）应用上述理论结果和软件工具来分析糖尿病和正常条件下的肝细胞代谢。这项研究将更深入地了解肝脏对糖尿病疾病状态的反应机制，从而为疾病治疗，监测和诊断提供新的策略。通过允许在同位素稳定之前的过渡期进行示踪剂研究，本项目开发的技术将允许在比传统方法更短的时间内获得通量估计。由于肝细胞的肝脏特异性功能通常会随着时间的推移而退化，因此在从肝脏中分离出这些细胞后立即对其进行分析以获得体内通量状态的准确图像非常重要。