项目名称: 胰岛素抵抗之动力学机理及全局整体研究
项目编号: No.61471186
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 无线电电子学、电信技术
项目作者: 王冠宇
作者单位: 南方科技大学
项目金额: 85万元
中文摘要: 人类现面临的一个巨大的危机是糖尿病的大规模流行。对胰岛素抵抗的原创性探索将为解决该危机带来希望。胰岛素抵抗是指机体由于缺乏对胰岛素的响应而导致的血糖吸收困难;被公认为二型糖尿病的病理基础。我们却提出一个反直觉的观点:胰岛素抵抗首先是一个必不可少的有用机制。在妊娠等特定条件下,即使重度的胰岛素抵抗也是必要的。从动力学角度出发,我们整合了前人对生物系统多层面的研究;并以此为基础提出了可调门限假说。我们将通过实验(分子生物和细胞图像实时观察)和计算(血糖-胰岛素负反馈系统的动力学模拟)两方面来验证和修正可调门限假说。我们将以AKT蛋白磷酸化为主要的胰岛素响应信号来分析细胞对胰岛素的响应是否遵循双稳和可调门限机理。我们将通过数学模拟来解释未得到合理解释的一些现象(反应性低血糖、妊娠期糖尿病、肥胖导致的胰岛素剂量响应的右平漂)。本项目将突破人们对糖尿病的思维定式,具有深远的科学意义和社会价值。
中文关键词: 生物分子信息检测;动力学模拟及仿真;细胞及分子生物;胰岛素信号通路;胰岛素抵抗
英文摘要: The pandemic of diabetes constitutes a major health care crisis. Original researches on insulin resistance would provide hopes of resolving the crisis. Insulin resistance is a pathological condition underlying type 2 diabetes, under which the body lacks responses to insulin, causing the difficulty of glucose disposal. Here we put forward a counterintuitive viewpoint: insulin resistance is a necessary mechanism in the first place; under extreme conditions such as pregnancy, even severe insulin resistance is necessary. From the perspective of dynamics, we integrate researches spanning multiple biological levels, on the basis of which we put forward the adjustable threshold hypothesis. We propose to verify the hypothesis through experiments (molecular biology and real-time cell imaging) and computation (dynamical modeling of the glucose-insulin feedback system). We will use AKT phosphorylation as the primary signal of insulin response to verify bistability and the mechanisms of adjustable threshold. We will use mathematical modeling to explain some poorly understood phenomena (reactive hypoglycemia, gestational diabetes, obesity induced right-shift of insulin dose-response). The project would change the mindset of people about diabetes and thus has profound scientific and social values.
英文关键词: Biomolecular signal detection;Dynamical modeling and simulation;Cellular and molecular biology;Insulin signaling pathway;Insulin resistance