The mission of the Stable Isotope &Metabolomics Core is to provide guided metabolite and substrate flux determinations in complex in vivo metabolic models in partnership with the Animal Physiology Core. The Stable Isotope &Metabolomics Core provides an array of in vitro metabolic methodologies that augment these 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 DRTC, the effects of defined pharmacological, dietary, environmental and genetic alterations are thoroughly characterized for their effects on glucose 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 in vivo and in vitro experimentation using a step-by-step guided approach in rodent, and other models. To accomplish these goals, the Stable Isotope &Metabolomics Core 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) detennine 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 camitine profiles;and 4) provide mentorship and protocol development in the use of 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. All 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.
The Stable Isotope &Metabolomics Core 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.
|Rudolph, Bryan; Bjorklund, Nicole; Ovchinsky, Nadia et al. (2018) Methods to improve the noninvasive diagnosis and assessment of disease severity in children with suspected nonalcoholic fatty liver disease (NAFLD): Study design. Contemp Clin Trials 75:51-58|
|Tang, Yan; Kwon, Hyokjoon; Neel, Brian A et al. (2018) The fructose-2,6-bisphosphatase TIGAR suppresses NF-?B signaling by directly inhibiting the linear ubiquitin assembly complex LUBAC. J Biol Chem 293:7578-7591|
|Chemaly, Elie R; Troncone, Luca; Lebeche, Djamel (2018) SERCA control of cell death and survival. Cell Calcium 69:46-61|
|Iqbal, Niloy Jafar; Lu, Zhonglei; Liu, Shun Mei et al. (2018) Cyclin-dependent kinase 4 is a preclinical target for diet-induced obesity. JCI Insight 3:|
|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|
|Racine, Jeremy J; Stewart, Isabel; Ratiu, Jeremy et al. (2018) Improved Murine MHC-Deficient HLA Transgenic NOD Mouse Models for Type 1 Diabetes Therapy Development. Diabetes 67:923-935|
|Shu, Jun; Santulli, Gaetano (2018) Update on peripheral artery disease: Epidemiology and evidence-based facts. Atherosclerosis 275:379-381|
|Zhao, Xiaoping; Zhao, Li; Yang, Hao et al. (2018) Pyruvate kinase M2 interacts with nuclear sterol regulatory element-binding protein 1a and thereby activates lipogenesis and cell proliferation in hepatocellular carcinoma. J Biol Chem 293:6623-6634|
|Qiu, Yunping; Moir, Robyn D; Willis, Ian M et al. (2018) Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for Investigation of Model Organism Metabolomes. Metabolites 8:|
|Liu, Shunmei; Marcelin, Genevieve; Blouet, Clemence et al. (2018) A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus. Mol Metab 8:37-50|
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