LIPID, LIPOPROTEIN, AND GLUCOSE METABOLISM CORE

脂质、脂蛋白和葡萄糖代谢核心

基本信息

批准号：
8879107
负责人：
PATRICK TSO
金额：
$ 25.82万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8879107
关键词：
Academic Medical Centers Age Animal Husbandry Animals B-Lymphocytes Beta Cell Bile Acids Biological Assay Body Composition Body Weight Breeding Cardiovascular Diseases Cause of Death Cell physiology Chemicals Chronic Diabetes Mellitus Diet Dyslipidemias Eating Energy Metabolism Fatty acid glycerol esters Functional disorder Funding Glucose Goals Human Impairment Institution Insulin Insulin Signaling Pathway Intestines Lipids Lipoproteins Lymph Measurement Metabolic Metabolism Methodology Methods Michigan Mus National Human Genome Research Institute Paper Peptides Performance Phenotype Physiological Plasma Predisposing Factor Procedures Process Production Publishing Research Personnel Resistance Role Sampling Schedule Services Technology Testing Tissues Transgenic Organisms Translations Universities Washington Work bariatric surgery diabetic feeding genetic manipulation glucose metabolism improved interest investigator training lipid metabolism meetings metabolomics mouse model novel strategies response

项目摘要

Diabetes is defined by abnormalities in circulating substrates; glucose is obvious, but dyslipidemias also typify the condition. Central to the impairment of substrate metabolism is beta-cell dysfunction and resistance to insulin action. There have been significant advances in recent years that have increased our understanding of normal and abnormal beta-cell function and great progress has been made in elucidating the insulin-signaling pathway. However, much work remains before translation of these advances to human diabetes. Transgenic technology holds great promise for making these connections but requires precise and often sophisticated phenotypic characterization to maximize information gained from appropriate mouse models. It is also clear that abnormalities in the production and metabolism of lipids and lipoproteins are common in diabetes, that they interact with the processes governing glucose metabolism, and most importantly, that they are predisposing factors for cardiovascular disease, the primary cause of death in diabetic humans. To meet the goals of the UC MMPC as well as the MMPC Consortium, we will continue to focus on the phenotypic analysis of lipid, lipoprotein, and glucose metabolism in mouse models in order to assist investigators in gaining an understanding of the effects of specific genetic manipulations and their role in diabetes. Four broad, long-range goals of the Lipid, Lipoprotein, and Glucose Metabolism Core (Core C) have been established: Specific Aim 1; To provide current state of the art phenotypic tests that allow investigators to characterize the lipid, lipoprotein, and glucose metabolism of their mice. Specific Aim 2: To advise investigators on the most appropriate tests, and the optimal sequence of tests, to meet specific goals of phenotypic characterization of their genetically modified mice, or how a physiological manipulation (e.g. chronic feeding of a high fat diet) modifies the response of the animal. Specific Aim 3: To train investigators in the performance of specialized procedures established and routinely practiced in the Core. Specific Aim 4: To improve current methods and develop new procedures and new approaches to study lipid and glucose metabolism in mice.

糖尿病的定义是循环基质异常；血糖是显而易见的，但血脂异常也是这种情况的典型代表。底物代谢受损的核心是β细胞功能障碍和对胰岛素作用的抵抗。近年来取得的重大进展增加了我们对正常和异常 β 细胞功能的了解，并且在阐明胰岛素信号通路方面也取得了巨大进展。然而，在将这些进步转化为人类之前，还有很多工作要做糖尿病。转基因技术为建立这些连接带来了巨大的希望，但需要精确且通常复杂的表型表征，以最大限度地从适当的小鼠模型中获得信息。同样清楚的是，脂质和脂蛋白的产生和代谢异常在糖尿病中很常见，它们与控制葡萄糖代谢的过程相互作用，最重要的是，它们是心血管疾病的诱发因素，心血管疾病是糖尿病患者死亡的主要原因。糖尿病人。为了实现 UC MMPC 以及 MMPC 联盟的目标，我们将继续关注小鼠模型中脂质、脂蛋白和葡萄糖代谢的表型分析，以帮助研究人员了解特定遗传因素的影响。操作及其在糖尿病中的作用。脂质、脂蛋白和葡萄糖代谢核心（核心 C）的四个广泛的长期目标已成立：具体目标1；提供当前最先进的表型测试，使研究人员能够表征小鼠的脂质、脂蛋白和葡萄糖代谢。具体目标 2：为研究人员提供最合适的测试和最佳测试顺序的建议，以满足转基因小鼠表型特征的特定目标，或生理操作（例如长期喂养高脂肪饮食）如何改变基因组小鼠的表型特征。动物的反应。具体目标 3：培训调查人员执行核心区建立和常规实施的专门程序。具体目标 4：改进现有方法并开发新程序和新方法来研究小鼠脂质和葡萄糖代谢。