Animal Studies

动物研究

• 批准号: 7331475
• 负责人: MICHAEL J. WELCH
• 金额: $ 27.71万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-15 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7331475
• 关键词: Address; Age; Aging; Agonist; Animal Model; Animals; Antidiabetic Drugs; Apoptosis; Cardiac; Cyclotrons; Diabetes Mellitus; Disease; Glucose; Heart Diseases; Human; Image; Ligands; Metabolic; Metabolism; Metformin; Modeling; Muscle; Mutation; Nicotinic Acids; Patients; Pharmacotherapy; Pioglitazone; Protein Overexpression; Radiochemistry; Radiopharmaceuticals; Rattus; Rodent; Rodent Model; Skeletal system; Sulfonylurea Compounds; Techniques; Technology; Tissues; Transgenic Mice; Treatment Protocols; Zucker Rats; diabetic; diabetic rat; fatty acid metabolism; genetic profiling; heart metabolism; human NOS2A protein; instrumentation; metabolic abnormality assessment; mouse model; non-diabetic; receptor; rosiglitazone

This project will take advantage of the techniques developed in old Project 1 to quantify glucose oxidative and fatty acid metabolism in the rodent. The project will utilize both rat (ZDF Zucker) and mouse models (MHC-PPAR or MCK-PPAR) of diabetes to evaluate in these well controlled models, the differences in metabolic profile between diabetic animals and normal controls as well as the effect of the therapies being utilized in humans in the instrumentation project. An important advantage of the animal model is the ability to evaluate the impact that genetic changes have on cardiac metabolism and other tissues resulting from these therapies. This project will also utilize animal models to validate the radiopharmaceuticals being developed in Project 1. The project will, therefore, interact with both other projects. The radiopharmaceuticals for the metabolism studies will be produced in the cyclotron/radiochemistry core and this project will take advantage of the advances in microPET technology being carried out in the instrumentation core. This project will address the general hypothesis that rodent models of cardiac disease in conjunction with microPET and microCT imaging can be used to evaluate metabolic changes in the disease as well as changes caused by drug therapies. To this aim we will evaluate three models of diabetes and selected therapies.

本项目将利用旧项目1中开发的技术来量化啮齿动物中的葡萄糖氧化和脂肪酸代谢。该项目将利用两个大鼠（ZDF Zucker）和糖尿病小鼠模型（MHC-PPAR或MCK-PPAR）中进行比较，以评价在这些良好控制的模型中，糖尿病动物和正常对照之间代谢谱的差异以及在仪器项目中用于人类的疗法的效果。动物模型的一个重要优势是能够评估遗传变化对心脏代谢和这些治疗产生的其他组织的影响。该项目还将利用动物模型来验证正在使用的放射性药物 在项目1中开发。因此，该项目将与其他两个项目相互作用。的 用于代谢研究的放射性药物将在回旋加速器/放射化学核心中生产，该项目将利用仪器核心中正在进行的微型PET技术的进步。该项目将解决心脏病啮齿动物模型结合microPET和microCT成像可用于评估疾病的代谢变化以及药物治疗引起的变化的一般假设。本 我们将评估三种糖尿病模型和选定的治疗方法。