Nonstationary Isotopic Tracer Analysis of Hepatocytes

项目描述（由申请人提供）：该项目有三个具体目标，即(a)开发基于非平稳同位素示踪实验的代谢通量估计方法，(b)创建用于分析和解释非平稳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情况下的肝细胞代谢。这项研究将提供对肝脏对糖尿病疾病状态的反应机制的更深层次的理解，从而导致疾病治疗，监测和诊断的新策略。通过允许在同位素稳定状态之前的瞬态期间进行示踪研究，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不久对其进行分析以准确了解体内通量状态是很重要的。

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.