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.

Public Health Relevance

The Stable Isotope & Metabolomics Core of the Einstein-Mount Sinai Diabetes Research Center provides cost effective, high quality resources that facilitate the scientific progress made by a large group of scientists committed to improve our understanding of the integrative physiology of diabetes in order to improve the treatment of patients with diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK020541-40
Application #
9174082
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Hyde, James F
Project Start
Project End
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
40
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine, Inc
Department
Type
DUNS #
079783367
City
Bronx
State
NY
Country
United States
Zip Code
10461
Lontchi-Yimagou, Eric; You, Jee Young; Carey, Michelle et al. (2018) Potential approaches to prevent hypoglycemia-associated autonomic failure. J Investig Med 66:641-647
Chemaly, Elie R; Troncone, Luca; Lebeche, Djamel (2018) SERCA control of cell death and survival. Cell Calcium 69:46-61
Wang, Peng; Karakose, Esra; Liu, Hongtao et al. (2018) Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells. Cell Metab :
Jeong, Jae Hoon; Chang, Ji Suk; Jo, Young-Hwan (2018) Intracellular glycolysis in brown adipose tissue is essential for optogenetically induced nonshivering thermogenesis in mice. Sci Rep 8:6672
Willis, Ian M; Moir, Robyn D; Hernandez, Nouria (2018) Metabolic programming a lean phenotype by deregulation of RNA polymerase III. Proc Natl Acad Sci U S A 115:12182-12187
Mao, Kai; Quipildor, Gabriela Farias; Tabrizian, Tahmineh et al. (2018) Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun 9:2394
Kumar, Anil; Katz, Liora S; Schulz, Anna M et al. (2018) Activation of Nrf2 Is Required for Normal and ChREBP?-Augmented Glucose-Stimulated ?-Cell Proliferation. Diabetes 67:1561-1575
Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J et al. (2018) HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression. J Immunol 200:3353-3363
Mitelman, Serge A; Bralet, Marie-Cecile; Mehmet Haznedar, M et al. (2018) Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia. Brain Imaging Behav 12:532-546
Rastogi, Deepa; Nico, John; Johnston, Andrew D et al. (2018) CDC42-related genes are upregulated in helper T cells from obese asthmatic children. J Allergy Clin Immunol 141:539-548.e7

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