The goal of the Stable Isotope and Metabolomics Core (SIMC) is to provide to Einstein-Mount Sinai Diabetes Research Center research investigators cost effective, efficient and robust platforms for the determination of metabolites/lipids designed to cover interlocking metabolite and lipid pathways, and help to improve our understanding of conditions which change fuel utilization and biosynthesis in cytosolic and mitochondrial metabolic pathways, i.e., glycolysis, pentose and tricarboxylic acid (TCA) cycles. To accomplish these goals in one facility, the SIMC has updated its technology infrastructure to include the latest Seahorse XFe24 and XFe96 Seahorse Flux Analyzers for assessment of glycolytic and mitochondrial energetics in real time, the latest Sciex 6500+ QTRAP with Selexion ion mobility for targeted LC/MS.MS metabolite and lipidomic analyses, and is due to replace its Orbitrap/LTQ high mass accuracy instrument with the latest Shimadzu LC-9030 quadrupole Time of Flight with Nexera UPLC for untargeted metabolomic and lipidomic analyses. These latest additions add to the high mass resolution Waters GC-TOF/MS and two unit Dalton resolution Agilent single quadrupole GC/MS machines to accomplish the following aims: 1. To determine metabolomic/lipidomic profiles for the diagnosis/characterization of physiological and pathophysiological states in cells, tissues and biofluids (plasma, urine, stool, etc.). 2. To perform in vivo stable isotope substrate assays to determine rates of protein synthesis, lipogenesis, peripheral glucose disposal, hepatic glucose recycling, glucose-glycerol cycling and Cori cycling, high energy phosphate (ATP, creatine phosphate) turnover, and in vitro stable isotope flux dissections of metabolic pathways. 3. To perform assessments of glycolysis (extracellular acidification rates, glycolytic ATP production rates) and mitochondrial oxygen consumption (mitochondrial respiration and mitochondrial ATP production rates) in tissue explants, primary isolated and tissue culture cells using Seahorse Biosciences Flux Analyzers. 4. To advise and instruct ES-DRC investigators and their students, fellows and technical staff in the design and interpretation of fluxomics, metabolomics/lipidomics and computational analyses with the aim of elucidating the molecular basis underlying glucose and lipid homeostasis in humans and animal models.
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