The goal of this P01 application is to develop novel therapies for the treatment of non insulin-dependent diabetes mellitus (NIDDM). We seek to team senior members for the Marjorie Touchstone Diabetes Center (Project 1, Unger and Project 2, Newgard) with colleagues from the Molecular Cardiology Center for Biomedical Inventions (Project 3, Johnston and Project 4, Kodadek) here at the University of Texas Southwestern Medical Center in Dallas (UTSWMC). These principal investigators will be complemented buy key co-investigators that will provide expertise in molecular biology (Mangelsdorf, Meidell), nuclear magnetic resonance (NMR) analysis of metabolism (Sherry, Jones), and physical methods for gene targeting (Grayburn). The proposal contains plans for basic biology research relating to the mechanics of hepatic, cardiovascular, and islet dysfunction in obesity and NIDDM (Projects 1 and 2). It also contains proposals for development of novel technologies for gene targeting, controlled regulation of gene expression by small molecules, and manipulation of protein/protein interactions (Projects 3 and 4). Several points of integration of the biology and technology development programs have been identified and will be exploited. The fundamental motivation for assembling a team of this type is that no comprehensive and complete therapy for NIDDM currently exists. Given the complexity of the disease and the alarming rise in its incidence towards epidemic proportions, a focused effort for creation of new therapeutic strategies is required. Integration of biological research with technology development as we are proposing here may allow achievement of this difficult goal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK058398-03
Application #
6524319
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Program Officer
Laughlin, Maren R
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$1,464,631
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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
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
Newgard, Christopher B (2017) Metabolomics and Metabolic Diseases: Where Do We Stand? Cell Metab 25:43-56

Showing the most recent 10 out of 181 publications