A short course: An organ systems approach to target the Metabolic syndrome

短期课程：针对代谢综合征的器官系统方法

• 批准号: 8065916
• 负责人: OWEN P MCGUINNESS
• 金额: $ 10.49万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8065916
• 关键词: Adrenergic Agents; Anesthesia and Analgesia; Animal Behavior; Animal Experimentation; Animal Model; Animals; Basic Science; Blood Pressure; Blood specimen; Body Composition; Canis familiaris; Cardiovascular Physiology; Cardiovascular system; Catheters; Cellular biology; Central obesity; Cholinergic Agents; Clinic; Communities; Conscious; Data; Data Quality; Defect; Diabetes Mellitus; Drug Kinetics; Dyslipidemias; Echocardiography; Educational process of instructing; Endocrine; Epidemic; Equilibrium; Euglycemic Clamping; Evaluation; Experimental Designs; Faculty; Feedback; Feeding behaviors; Frequencies; Generations; Genetic; Glucose; Glucose Clamp; Glucose tolerance test; Guidelines; Hand; Health; Healthcare Systems; Homeostasis; Hormones; Human Resources; Hypertension; Image; In Vitro; Indirect Calorimetry; Institutes; Institution; Insulin; Insulin Resistance; Intervention; Kinetics; Knowledge; Laboratories; Learning; Lipids; Liver; Macronutrients Nutrition; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic syndrome; Metabolism; Mus; Neurologic; Obesity; Operative Surgical Procedures; Organ; Outcome; Pathogenesis; Pathology; Perfusion; Personal Satisfaction; Pharmacology; Pharmacotherapy; Phenotype; Physiological; Physiology; Plasma; Prevalence; Procedures; Process; Recording of previous events; Regulation; Research; Research Infrastructure; Research Personnel; Research Training; Resource Sharing; Resources; Risk Factors; Science; Stroke; Students; System; Tail; Techniques; Telemetry; Testing; Tissues; Training; Training Programs; Translational Research; Ultrasonography; Veins; Very low density lipoprotein; animal care; behavior test; bench to bedside; body system; design; drug discovery; energy balance; experience; feeding; glucose metabolism; graduate student; heart disease risk; hemodynamics; human disease; improved; in vivo; investigator training; islet; lectures; metabolic abnormality assessment; neurobehavioral; programs; response; skills; therapeutic target; tool

DESCRIPTION (provided by applicant): This application is in response to RFA GM-08-010 (Short Courses in Integrative and Organ Systems Pharmacology). A two-week short course entitled, an organ systems approach to experimental targeting of the Metabolic Syndrome is proposed. The Metabolic Syndrome is a cluster of metabolic risk factors that when they occur together increase the risk of heart disease, stroke and diabetes. These risk factors include insulin resistance, central obesity, dyslipidemia and hypertension. The Metabolic Syndrome is an epidemic and its prevalence is still on the rise. The demands on the US Health Care System resulting from its pathology are debilitating to the economy. Clearly, there is a need to understand the pathogenesis of the Metabolic Syndrome and learn ways to treat it. This is challenging because it is a condition that involves organ system cross talk and understanding it requires knowledge of integrated physiology. Over the last 30 years physiology and pharmacology graduate programs have shifted their emphasis to cell biology. Consequently, there is a generation of physiologists and pharmacologists that lack experience in organ system physiology. Thus, there is a great need to restore and contemporize the toolbox for the study of integrated physiology. The objective of the course will be to give students the tools needed to assess whether an experimental intervention (pharmacologic, genetic, dietary, or environmental) alters macronutrient metabolism, energy balance, cardiovascular homeostasis or animal behavior. Moreover students will learn how to measure whole body and tissue specific kinetics, the principles of which can be applied to the kinetics of drugs, substrates and hormones. To accomplish this we will use a combination of lectures, hands on laboratories, demonstrations and data problem sessions. Three guiding principles thread through the course components. 1) organ systems do not function in isolation; 2) primary mechanisms can best be identified by disrupting compensatory feedback loops using tools such as a "glucose clamp." 3) proper animal care is critical to good outcomes. With regard to the last the privilege of animal research is accompanied by the responsibility of treating animals humanely. Students will learn that the quality of data obtained in animal models is directly related to the health and well-being of the animals. All procedures involving animals will follow USDA and AAALAC guidelines. Vanderbilt is the ideal place to conduct such a course. Vanderbilt has a strong history in the physiologic regulation of metabolic, hemodynamic, neurobehavioral processes, and pharmacological testing. Vanderbilt is internationally recognized for its excellence in translational research that uses bench to bedside research to improve drug therapy for human disease. The Vanderbilt Metabolic Physiology Shared Resource (VMPSR) is comprised of core resources of the Vanderbilt Diabetes Research and Training Center (VDRTC) and the Vanderbilt Mouse Metabolic Phenotyping Center (VMMPC) and will provide infrastructure for the course. VMPSR personnel have extensive experience with experimental surgery and procedures for studying metabolism and cardiovascular function in vivo. Organ system approaches will be used to study metabolic flux, endocrine function, animal behavior and cardiovascular function in conscious animals and these will be correlated with results in vitro systems. The VMMPC gives a course annually in which it teaches the skills necessary to assess insulin action in mice. This course has attracted investigators from all over the world. We will use this experience in developing An organ systems approach to experimental targeting of the Metabolic Syndrome. Vanderbilt also has strong Murine Neurobehavioral Core Laboratories and a state of the art imaging institute that actively support both basic research and drug discovery programs. We will combine the strengths of the Vanderbilt community with faculty from other institutions in the national MMPC program to provide a comprehensive course for students to learn how to study the Metabolic Syndrome and its components in animals. PUBLIC HEALTH RELEVANCE: The purpose of this course is to train investigators to do studies in animals so they can effectively develop and evaluate therapeutic targets to treat diabetes and obesity before they enter the clinic. Most graduate students in the basic biomedical sciences receive limited training in physiology and integrative pharmacology. The benefit to human disease is that these trainees will now be equipped with the tools necessary to fill a void in our training programs.

描述（由申请人提供）：本申请是对 RFA GM-08-010（综合和器官系统药理学短期课程）的回应。提出了为期两周的短期课程，题为“代谢综合征实验目标的器官系统方法”。代谢综合症是一组代谢危险因素，当它们同时出现时，会增加患心脏病、中风和糖尿病的风险。这些危险因素包括胰岛素抵抗、中心性肥胖、血脂异常和高血压。代谢综合症是一种流行病，其患病率仍在上升。美国医疗保健系统的病态造成的需求正在削弱经济。显然，有必要了解代谢综合征的发病机制并学习治疗方法。这是具有挑战性的，因为它是一种涉及器官系统串扰的疾病，理解它需要综合生理学的知识。在过去的 30 年里，生理学和药理学研究生课程已将重点转向细胞生物学。因此，一代生理学家和药理学家缺乏器官系统生理学经验。因此，非常需要恢复和现代化综合生理学研究的工具箱。该课程的目标是为学生提供评估实验干预（药理学、遗传、饮食或环境）是否改变宏量营养素代谢、能量平衡、心血管稳态或动物行为所需的工具。此外，学生将学习如何测量全身和组织的特定动力学，其原理可应用于药物、底物和激素的动力学。为了实现这一目标，我们将结合讲座、实验室实践、演示和数据问题会议。三个指导原则贯穿课程组成部分。 1）器官系统并不是孤立运作的； 2）主要机制可以通过使用“葡萄糖钳”等工具破坏补偿反馈回路来最好地识别。 3) 适当的动物护理对于良好的结果至关重要。最后，动物研究的特权伴随着人道对待动物的责任。学生将了解到，动物模型中获得的数据的质量与动物的健康和福祉直接相关。所有涉及动物的程序都将遵循 USDA 和 AAALAC 指南。范德比尔特是举办此类课程的理想场所。范德比尔特在代谢、血流动力学、神经行为过程和药理学测试的生理调节方面拥有悠久的历史。范德比尔特大学因其在转化研究方面的卓越表现而获得国际认可，该研究利用从实验室到临床的研究来改善人类疾病的药物治疗。范德比尔特代谢生理学共享资源 (VMPSR) 由范德比尔特糖尿病研究和培训中心 (VDRTC) 和范德比尔特小鼠代谢表型中心 (VMMPC) 的核心资源组成，将为该课程提供基础设施。 VMPSR 人员在研究体内代谢和心血管功能的实验手术和程序方面拥有丰富的经验。器官系统方法将用于研究有意识动物的代谢通量、内分泌功能、动物行为和心血管功能，这些将与体外系统的结果相关联。 VMMPC 每年都会开设一门课程，教授评估小鼠胰岛素作用所需的技能。该课程吸引了来自世界各地的研究人员。我们将利用这一经验开发一种器官系统方法，以实验性靶向代谢综合征。范德比尔特大学还拥有强大的小鼠神经行为核心实验室和最先进的成像研究所，积极支持基础研究和药物发现项目。我们将把范德比尔特社区的优势与国家 MMPC 项目中其他机构的教师结合起来，为学生提供全面的课程，让他们学习如何研究动物的代谢综合症及其组成部分。公共卫生相关性：本课程的目的是培训研究人员在动物身上进行研究，以便他们能够在进入临床之前有效地开发和评估治疗糖尿病和肥胖症的治疗靶点。大多数基础生物医学研究生只接受有限的生理学和综合药理学培训。对人类疾病的好处是，这些学员现在将配备必要的工具来填补我们培训计划中的空白。