Stable Isotope & Metabolomics Core

稳定同位素

基本信息

批准号：
8872950
负责人：
Irwin Jack Kurland
金额：
$ 12.97万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-10 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8872950
关键词：
Acyl Coenzyme A Adipocytes Affect Aging Amino Acids Anabolism Animal Model Animals Beta Cell Biochemical Biochemical Pathway Biological Assay Biological Markers Biological Models Caloric Restriction Carnitine Cell Line Cells Citric Acid Cycle Clinical Complement Complex Core Facility Data Development Diabetes Mellitus Diagnosis Diet Disease Evaluation Exercise Fatty Acids Gene Targeting Genus Hippocampus Glucose Glycerol Glycolysis Goals Hepatic Hepatocyte Homeostasis Human Hypothalamic structure In Vitro Insulin Insulin Resistance Investigation Lipids Measurement Mentorship Metabolic Metabolic Diseases Metabolic Pathway Metabolism Methodology Methods Mission Mitochondria Molecular Mutation Neurons Obesity Organ Organelles Oxygen Consumption Pathway interactions Patients Pentosephosphates Pentoses Peripheral Phospholipids Physiological Physiology Plasma Postdoctoral Fellow Protein Biosynthesis Recording of previous events Recycling Regulation Research Research Personnel Resources Respiration Rodent Rodent Model Role Scientist Sense Organs Services Skeletal Muscle Students System Systems Biology Testing Tissues Urine Work Yeasts base blood glucose regulation clinical investigation complement C2b cost effective cost effectiveness design detection of nutrient extracellular fly glucose disposal glucose metabolism high throughput screening improved in vivo insulin sensitivity interest lipid biosynthesis lipid metabolism mass spectrometer meetings member metabolomics microbiome protein metabolism protocol development stable isotope tissue culture tissue/cell culture translational study

项目摘要

The mission of the Stable Isotope & Metabolomics Core (SIMC) is to provide guided metabolite and substrate flux determinations in complex in vivo metabolic rodent models and for human clinical investigation for members of the Einstein-Mount Sinai Diabetes Research Center (ES-DRC). The SIMC provides an array of in vitro metabolic methodologies that augment in vivo investigations. These services provide investigators with specialized assays to determine substrate flux dynamics and metabolite profiles at the organelle, cellular, tissue and whole body level thereby elucidating the integrative network of disorders in glucose, protein and lipid metabolism. Through these collaborative efforts with the other Cores of the ES-DRC, the effects of defined pharmacological, dietary, environmental and genetic alterations are thoroughly characterized for their effects on glucose and lipid homeostasis, insulin action, and metabolism. The role of candidate molecules in relevant tissues (i.e., neurons, hepatocytes, skeletal muscle, adipocytes and beta cells) that are related to glucose homeostasis can be specifically delineated by thorough and definitive analyses using in vivo and in vitro experimentation with a step-wise guided approach in rodents and humans as well as in cell lines. To accomplish these goals, the SIMC will: 1) perform in vivo stable isotope substrate flux assays for the determination of rates of protein synthesis, lipogenesis, peripheral glucose disposal, hepatic glucose recycling, glucose-glycerol cycling and glucose-lactate cycling; 2) determine glycolysis (extracellular acidification rates) and mitochondrial oxygen consumption (mitochondrial respiration) in isolated cells, tissue explants or tissue culture, using Seahorse Biosciences Flux Analyzers, as well as more comprehensive stable isotope flux assessments; 3) perform targeted hypothesis-driven assessments of plasma and tissue metabolite profiles for key metabolites in the glycolytic/gluconeogenic, pentose phosphate, and tricarboxylic (TCA) cycle pathways, and lipid metabolism, including fatty acid, fatty acyl CoA and fatty acyl carnitine profiles; 4) provide mentorship and assistance with protocol development , which uses mass spectrometer-based flux and metabolite profiling methods for the evaluation of molecular biochemical targets relevant to the control of glucose and fatty acid homeostasis; and 5) coordinate these efforts with other ES-DRC and Institutional Core facilities at Einstein and Mount Sinai. All of these services are available to investigators new to diabetes research, as well as to investigators working on diabetes-related projects that can be enriched and extended by the use of the expertise and facilities of this Core.

稳定的同位素和代谢组学核心（SIMC）的任务是提供指导的代谢物和底物复杂体内代谢啮齿动物模型的通量确定和人类的临床研究爱因斯坦-Mount西奈糖尿病研究中心（ES-DRC）的成员。 SIMC提供了一个In的数组增强体内研究的体外代谢方法。这些服务为调查人员提供了专门的测定法以确定细胞器中的底物通量动力学和代谢产物轮廓组织和全身水平，从而阐明葡萄糖，蛋白质和脂质代谢。通过与ES-DRC的其他核心的这些合作努力，定义的效果药理学，饮食，环境和遗传改变的作用是彻底特征的关于葡萄糖和脂质稳态，胰岛素作用和代谢。候选分子在相关的作用与葡萄糖有关的组织（即神经元，肝肌，骨骼肌，脂肪细胞和β细胞）可以通过体内和体外进行彻底和确定的分析来专门划定稳态在啮齿动物和人类以及细胞系中使用逐步引导的方法进行实验。到实现这些目标，SIMC将：1）在体内稳定同位素底物通量测定确定蛋白质合成的速率，脂肪生成，外周葡萄糖处置，肝葡萄糖回收，葡萄糖 - 甘油循环和葡萄糖乳酸循环； 2）确定糖酵解（细胞外酸化速率）分离的细胞，组织外植体或组织中的线粒体氧消耗（线粒体呼吸）培养，使用Seahorse Biosciences通量分析仪，以及更全面的同位素通量评估； 3）对血浆和组织代谢产物轮廓进行有针对性的假设驱动评估糖酵解/糖素异生，五磷酸五氧化苯甲酸酯和三羧基（TCA）循环途径中的关键代谢产物，和脂质代谢，包括脂肪酸，脂肪酰基COA和脂肪酰基肉碱谱； 4）提供指导以及协议开发的协助，该协议使用基于质谱仪的通量和代谢物分析评估与葡萄糖和脂肪酸控制的分子生化靶标的方法稳态； 5）与爱因斯坦的其他ES-DRC和机构核心设施协调这些努力西奈山。所有这些服务均可提供新的糖尿病研究的调查人员，以及从事与糖尿病相关项目的研究人员可以通过使用可以丰富和扩展该核心的专业知识和设施。