The Yale Mouse Metabolic Phenotyping Center (MMPC) was established in the spring of 2000 with the mission to advance research in the area of diabetes by providing novel experimental tools to the scientific community for phenotyping mouse transgenic models of diabetes and related disorders using state-of-the-art methodology that is not widely available. The goals of this program are to: 1) broaden the scope of techniques available to investigators;2) standardize key methodologies;3) expedite the completion of research;and 4) compile and make accessible phenotyping data to the scientific community upon its publication or two years after the completion of phenotyping services, and 5) develop novel methodology for phenotyping transgenic mice through an national administered Pilot &Feasibility Program. The cornerstone of the Yale MMPC is its two research cores, the Integrative Physiology Core and the Metabolomics Core. The Integrative Physiology Core performs glucose-insulin clamps using both radioactive and stable isotope technology to assess insulin action in liver, skeletal muscle and fat of awake mice. This core also performs hyperglycemic clamps to assess in vivo B-cell function as well as hypoglycemic clamps to assess complications relating to defective glucose counter-regulation. This core also performs 24-hour, automated, non-invasive assessment of activity, food/water consumption and energy expenditure in an environmentally controlled room. The Integrative Physiology Core also contains a Mouse Imaging Sub-Core, which performs state-of-the-art noninvasive measurements of intracellular metabolites in muscle, liver and brain of transgenic mice using MRI methods which in turn is used to assess in vivo metabolic flux through critical biochemical pathways as well as whole body measurement of fat and muscle tissue with MRI. The Metabolomics Core provides automated high throughput clinical chemistry analyses of microliter samples of mouse plasma and urine. In addition this core provides state-of-the-art GC-MS and LC/MS/MS analysis of plasma, urine and tissue samples obtained from transgenic mice. The Animal Care Core provides a centralized facility for coordinating the import, initial quarantine, screening and monitoring of mice. This Core provides stable, biocontainment housing, husbandry and health care for mice submitted to the Center and determines the microbiological profile of each imported cohort. The Administrative Core oversees the operation of the Center, coordinates the importation of all mice to Yale, performs all of the material transfer agreements, coordinates and schedules meetings and teleconferences between investigators and MMPC Core Directors, coordinates the Pilot &Feasibility Program and administers the Enrichment Program. Overall the Yale MMPC serves as a national research center that provides investigators both inside and outside Yale access to unique, state-of-the-art, standardized methods to further characterize their novel transgenic mouse models of complex metabolic diseases in a cost efficient manner.

Public Health Relevance

It is anticipated that the results obtained from characterizing these mice at the Yale MMPC will provide important new insights into the pathogenesis and complications relating to diabetes and obesity in humans.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Resource-Related Research Projects--Cooperative Agreements (U24)
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Special Emphasis Panel (ZDK1-GRB-S (M1))
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Abraham, Kristin M
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Stark, Romana; Guebre-Egziabher, Fitsum; Zhao, Xiaojian et al. (2014) A role for mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) in the regulation of hepatic gluconeogenesis. J Biol Chem 289:7257-63
Befroy, Douglas E; Perry, Rachel J; Jain, Nimit et al. (2014) Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy. Nat Med 20:98-102
Perry, Rachel J; Zhang, Xian-Man; Zhang, Dongyan et al. (2014) Leptin reverses diabetes by suppression of the hypothalamic-pituitary-adrenal axis. Nat Med 20:759-63
Giménez-Cassina, Alfredo; Garcia-Haro, Luisa; Choi, Cheol Soo et al. (2014) Regulation of hepatic energy metabolism and gluconeogenesis by BAD. Cell Metab 19:272-84
Lee, Hui-Young; Gattu, Arijeet K; Camporez, João-Paulo G et al. (2014) Muscle-specific activation of Ca(2+)/calmodulin-dependent protein kinase IV increases whole-body insulin action in mice. Diabetologia 57:1232-41
Wheeler, Sadie G; Hammond, Christine L; Jornayvaz, François R et al. (2014) Ost?-/- mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity. Am J Physiol Gastrointest Liver Physiol 306:G425-38
Tao, Hanlin; Zhang, Yong; Zeng, Xiangang et al. (2014) Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med 20:1263-9
Perry, Rachel J; Samuel, Varman T; Petersen, Kitt F et al. (2014) The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510:84-91
Madiraju, Anila K; Erion, Derek M; Rahimi, Yasmeen et al. (2014) Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 510:542-6
Sajan, Mini P; Ivey 3rd, Robert A; Lee, Mackenzie et al. (2014) PKC? haploinsufficiency prevents diabetes by a mechanism involving alterations in hepatic enzymes. Mol Endocrinol 28:1097-107

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