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.

稳定同位素和代谢组学核心 (SIMC) 的使命是提供引导代谢物和底物复杂体内代谢啮齿动物模型中的通量测定以及人类临床研究爱因斯坦西奈山糖尿病研究中心（ES-DRC）的成员。 SIMC 提供了一系列增强体内研究的体外代谢方法。这些服务为调查人员提供专门的测定，以确定细胞器、细胞、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 其他核心的合作努力，所定义的效果药物、饮食、环境和遗传改变的影响已得到彻底表征对葡萄糖和脂质稳态、胰岛素作用和代谢的影响。候选分子在相关中的作用与葡萄糖相关的组织（即神经元、肝细胞、骨骼肌、脂肪细胞和β细胞）体内平衡可以通过体内和体外的彻底和明确的分析来具体描述在啮齿动物和人类以及细胞系中进行逐步引导方法的实验。到为了实现这些目标，SIMC 将：1) 进行体内稳定同位素底物通量测定测定蛋白质合成、脂肪生成、外周葡萄糖处理、肝葡萄糖回收率、葡萄糖-甘油循环和葡萄糖-乳酸循环； 2) 测定糖酵解（细胞外酸化率）和分离细胞、组织外植体或组织中的线粒体耗氧量（线粒体呼吸）使用 Seahorse Biosciences 通量分析仪以及更全面的稳定同位素通量进行培养评估； 3) 对血浆和组织代谢物谱进行有针对性的假设驱动评估糖酵解/糖异生、磷酸戊糖和三羧酸 (TCA) 循环途径中的关键代谢物，和脂质代谢，包括脂肪酸、脂酰辅酶A和脂酰肉碱谱； 4）提供指导并协助方案开发，该方案使用基于质谱仪的通量和代谢物分析与葡萄糖和脂肪酸控制相关的分子生化目标的评价方法体内平衡； 5) 与爱因斯坦的其他 ES-DRC 和机构核心设施协调这些工作西奈山。所有这些服务都可供糖尿病研究新手以及从事糖尿病相关项目的研究人员可以通过使用该核心的专业知识和设施。