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.

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 #
5U24DK059635-07
Application #
8333944
Study Section
Special Emphasis Panel (ZDK1-GRB-S (M1))
Program Officer
Abraham, Kristin M
Project Start
2001-03-01
Project End
2016-05-31
Budget Start
2012-07-01
Budget End
2013-05-31
Support Year
7
Fiscal Year
2012
Total Cost
$840,442
Indirect Cost
$363,034
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Petersen, Max C; Madiraju, Anila K; Gassaway, Brandon M et al. (2016) Insulin receptor Thr1160 phosphorylation mediates lipid-induced hepatic insulin resistance. J Clin Invest 126:4361-4371
Zaha, Vlad G; Qi, Dake; Su, Kevin N et al. (2016) AMPK is critical for mitochondrial function during reperfusion after myocardial ischemia. J Mol Cell Cardiol 91:104-13
Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I (2016) Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis. Diabetologia 59:933-7
Li, Yuanyuan; Tian, Xin; Ma, Ming et al. (2016) Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts. J Am Soc Nephrol 27:3628-3638
Kumamoto, Yosuke; Camporez, Joao Paulo G; Jurczak, Michael J et al. (2016) CD301b(+) Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha. Immunity 45:583-96
Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R et al. (2016) Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice. Am J Physiol Endocrinol Metab 311:E105-16
Khan, Nayaab S; Song, Chi Young; Thirunavukkarasu, Shyamala et al. (2016) Cytosolic Phospholipase A2α Is Essential for Renal Dysfunction and End-Organ Damage Associated With Angiotensin II-Induced Hypertension. Am J Hypertens 29:258-65
Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin et al. (2016) Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression. EMBO Mol Med 8:712-28
Perry, Rachel J; Borders, Candace B; Cline, Gary W et al. (2016) Propionate Increases Hepatic Pyruvate Cycling and Anaplerosis and Alters Mitochondrial Metabolism. J Biol Chem 291:12161-70
Pesta, Dominik H; Tsirigotis, Dimitrios N; Befroy, Douglas E et al. (2016) Hypophosphatemia promotes lower rates of muscle ATP synthesis. FASEB J 30:3378-3387

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