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 #
5U24DK059635-09
Application #
8708029
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
9
Fiscal Year
2014
Total Cost
$381,090
Indirect Cost
$152,207
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

Showing the most recent 10 out of 255 publications