The Integrative Physiology Core is designed to conduct in vivo and in vitro experiments and analytical assays to characterize metabolic phenotypes of transgenic/knock-out mouse models potentially useful for understanding diabetes, its complications, obesity and related metabolic diseases or conditions. The primary purpose of the integrative physiology core is to provide comprehensive standardized in vivo and in vitro procedures, accuracy of sample and data analysis, assistance in the design of experiments and interpretation of results to better understand the mechanisms of diabetes, its complications, obesity and related metabolic diseases or conditions for NIH grantees and others, both inside and outside the institution, who wish to characterize metabolic and physiologic alterations that may occur in mice. The Integrative Physiology Core provides highly skilled staff and state-of-the-art instrumentation to provide the most accurate, precise and reproducible in vivo glucose-insulin clamp results with the highest success rate. The principal functions of the Integrative Physiology Core are to provide NIH grantees and others, both inside and outside Yale, a state-of-the-art centralized facility for: 1) In Vivo assessment of insulin action and b-cell function in awake and unrestrained mice using hyperinsulinemic-euglycemic clamp and hyperglycemic clamp experiments, respectively, 2) In Vivo assessment of counter regulatory responses to hypoglycemia, 3) In Vivo assessment of muscle mitochondrial function by ^V and C NMR spectroscopy, 4) Implementation of exercise/training via swimming or treadmill models to assess the metabolic effects of exercise on glucose metabolism. 5) Access to state-of-the-art metabolic mouse imaging by SPECT/PET and MRI, 6) Assessment of transgenic/knockout mouse activity, food and water consumption, and energy expenditure using comprehensive mouse metabolic cages (Columbus Instruments), 7) Preparation of mouse tissue extracts and plasma samples for biochemical (GC-MS, LC/MS/MS, NMR) and molecular analysis in collaboration with the Yale MMPC Metabolomics Core, 8) Performance of in vivo analysis of body composition in mice using Proton NMR spectroscopy, 9) Preparation and characterization of glucose uptake in isolated epitrochelaris muscle, 10) Determination of rates of glucose-stimulated insulin secretion from isolated pancreatic islets, 11) Evaluation of substrate oxidative and non-oxidative metabolism in mouse hepatocyte suspensions, 12) Assistance in the design of in vivo and in vitro experiments and interpretation of in vivo and in vitro experiment results

Public Health Relevance

The Integrative Physiology Core is designed to conduct in vivo and in vitro experiments and analytical assays to characterize metabolic phenotypes of transgenic/knock-out mouse models potentially useful for understanding diabetes, its complications, obesity and related metabolic diseases or conditions.

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 #
8517665
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
$487,631
Indirect Cost
$194,240
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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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