The Metabolomics Core provides a facility to determine the phenotype of metabolite and hormone profiles of transgenic mouse models of diabetes and its complications. The services provided by the Metabolomics Core include the extraction, purification, derivatization, and instrumental analysis of metabolites, hormones, and selected enzyme activities from tissues and plasma. The methods have been scaled to account for the minimal amounts of tissues (-10 to 25 mg, and plasma volumes of - 5 to 25 pi) that can be provided by investigators.. The facility is equipped with an array of state-of-the-art instrumentation, including GC-MS, LC/MS/MS, HPLC, and NMR, providing the flexibility and resources for analyses of metabolite concentrations as well as sotopic enrichments. Metabolic panels of serum, plasma, and urine, including Chem 7, liver function tests lipid profiles, and divalent cations, are obtained using the COBAS MIRA system. We have optimized the COBAS Mira analytical system for analysis of mouse samples such that required volumes average -20 pi of serum for any combination of 4 tests. These plasma chemistry assays fill a need with very high demand for mouse studies, as reflected in our work flow over the last funding period. GC/MS and LC/MS/MS analyses provide complete profiles of chain length distribution of fatty acid metabolites, included free fatty acids, fatty acyl-CoA esters, diacylglycerols, ceramides. Other LC/MS/MS that are offered and are in high-demand include intermediates of glucose metabolism for metabolic flux measurements, and creatinines for renal clearance. The Metabolomics Core is a resource lab for the analysis of samples generated during the course of experiments of the Integrative Physiology Core at the Yale MMPC, and also provides the same array of assays to other outside investigators to assist in phenotyping of transgenic mouse models of diabetes Samples are analyzed on a fee-for-service basis with the charge per assay based on policy determined by the National MMPC Executive Committee, designed to provide substantial savings to NIH-funded users compared to commercial vendors. The Core has an active Research and Development Program to develop new analytical protocols to address new and exciting developments in the biochemistry of diabetes, obesity, and associated complications

Public Health Relevance

The Core has an active Research and Development Program to develop new analytical protocols to address new and exciting developments in the biochemistry of diabetes, obesity, and associated complications

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DK059635-08
Application #
8517666
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
8
Fiscal Year
2013
Total Cost
$194,108
Indirect Cost
$77,526
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Qiu, Yang; Perry, Rachel J; Camporez, João-Paulo G et al. (2018) In vivo studies on the mechanism of methylene cyclopropyl acetic acid and methylene cyclopropyl glycine-induced hypoglycemia. Biochem J 475:1063-1074
Budatha, Madhusudhan; Zhang, Jiasheng; Zhuang, Zhen W et al. (2018) Inhibiting Integrin ?5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. J Am Heart Assoc 7:
Jelenik, Tomas; Flögel, Ulrich; Álvarez-Hernández, Elisa et al. (2018) Insulin Resistance and Vulnerability to Cardiac Ischemia. Diabetes 67:2695-2702
Corbit, Kevin C; Camporez, João Paulo G; Edmunds, Lia R et al. (2018) Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body Composition, Liver Lipid Content, and Hepatic Insulin Signaling. Diabetes 67:208-221
Perry, Rachel J; Peng, Liang; Cline, Gary W et al. (2018) Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes. Cell Metab 27:210-217.e3
Majtan, Tomas; Jones Jr, Wendell; Krijt, Jakub et al. (2018) Enzyme Replacement Therapy Ameliorates Multiple Symptoms of Murine Homocystinuria. Mol Ther 26:834-844
Perry, Rachel J; Wang, Yongliang; Cline, Gary W et al. (2018) Leptin Mediates a Glucose-Fatty Acid Cycle to Maintain Glucose Homeostasis in Starvation. Cell 172:234-248.e17
Lawan, Ahmed; Min, Kisuk; Zhang, Lei et al. (2018) Skeletal Muscle-Specific Deletion of MKP-1 Reveals a p38 MAPK/JNK/Akt Signaling Node That Regulates Obesity-Induced Insulin Resistance. Diabetes 67:624-635
Vatner, Daniel F; Goedeke, Leigh; Camporez, Joao-Paulo G et al. (2018) Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents. Diabetologia 61:1435-1446
Wang, Yongliang; Nasiri, Ali R; Damsky, William E et al. (2018) Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer. Cell Rep 24:47-55

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