The overarching goal of this program project grant (PPG) continues to be the development of novel therapies for type 2 diabetes. The program has evolved from its genesis in 1999 as a collaboration between three research Centers within the University of Texas Southwestern Medical Center in Dallas (UTSWMC) to its current format, involving collaboration of four Centers located at UTSWMC and Duke University Medical Center. The program will continue with its unique format of melding projects on diabetes mechanisms with projects focused on development of new technologies for studying and treating the disease. In the past funding cycle, the most compelling advances have occurred in the area of pancreatic islet biology and related technologies. We have therefore chosen to focus the competitive renewal of this application on development of new strategies for understanding and reversing beta-cell dysfunction of type 2 diabetes. Project 1 (Newgard) will investigate novel pathways for control of beta-cell function and growth that have emerged in the prior funding period, particularly the role of the homeodomain transcription factor Nkx6.1 in the biology of normal and dysfunctional mature islet cells. Project 2 (Sherry) seeks to develop novel PET and MR agents for molecular imaging of islet beta-cells in vivo. Project 3 (Kodadek) will create cell permeable synthetic molecules capable of activating the expression of specific performance- or growth-enhancing genes in islet beta-cells. These projects will be supported by an Administrative Core (Core A), an Islet Targeting Core (Core B), which deploys two novel technologies for delivery of molecular cargo to islet beta-cells in living animals, and a Metabolomics Core (Core C), which provides state-of-the-art mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based technologies for comprehensive metabolic profiling and measurement of metabolic flux.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
3P01DK058398-09S1
Application #
7990555
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M3))
Program Officer
Blondel, Olivier
Project Start
2000-09-01
Project End
2010-02-28
Budget Start
2009-12-11
Budget End
2010-02-28
Support Year
9
Fiscal Year
2010
Total Cost
$28,960
Indirect Cost
Name
Duke University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
McGarrah, Robert W; Crown, Scott B; Zhang, Guo-Fang et al. (2018) Cardiovascular Metabolomics. Circ Res 122:1238-1258
Fisher-Wellman, Kelsey H; Davidson, Michael T; Narowski, Tara M et al. (2018) Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes. Cell Rep 24:3593-3606.e10
Jin, Eunsook S; Lee, Min Hee; Murphy, Rebecca E et al. (2018) Pentose phosphate pathway activity parallels lipogenesis but not antioxidant processes in rat liver. Am J Physiol Endocrinol Metab 314:E543-E551
Ren, Jimin; Shang, Ty; Sherry, A Dean et al. (2018) Unveiling a hidden 31 P signal coresonating with extracellular inorganic phosphate by outer-volume-suppression and localized 31 P MRS in the human brain at 7T. Magn Reson Med 80:1289-1297
An, Jie; Wang, Liping; Patnode, Michael L et al. (2018) Physiological mechanisms of sustained fumagillin-induced weight loss. JCI Insight 3:
Peterson, Brett S; Campbell, Jonathan E; Ilkayeva, Olga et al. (2018) Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or ? Cell Metabolism in the Absence of Overnutrition. Cell Rep 24:209-223.e6
White, Phillip J; McGarrah, Robert W; Grimsrud, Paul A et al. (2018) The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell Metab 27:1281-1293.e7
Jin, Eunsook S; Browning, Jeffrey D; Murphy, Rebecca E et al. (2018) Fatty liver disrupts glycerol metabolism in gluconeogenic and lipogenic pathways in humans. J Lipid Res 59:1685-1694
Shantavasinkul, Prapimporn Chattranukulchai; Muehlbauer, Michael J; Bain, James R et al. (2018) Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid. Surg Obes Relat Dis 14:1126-1132
Newgard, Christopher B (2017) Metabolomics and Metabolic Diseases: Where Do We Stand? Cell Metab 25:43-56

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