Diabetes mellitus is a complex disease in which the primary clinical symptom is abnormally high levels of plasma glucose. It may affect up to 5% of the human population. The major regulatory hormones that control glucose homeostasis are insulin and glucagon. Both hormones are expressed only in islet cells of the pancreas. In order to understand why insulin genes are only expressed in islet cells, it is necessary to develop a cell-free system to identify all the necessary components required for the expression of this important gene. Once these components are identified, one can then study their mechanism of action. In this proposal, we design experiments to identify, isolate and study the mechanism of action of transcription factors required for the expression of the insulin gene. These studies will involve various aspects of biochemistry, protein chemistry, molecular biology, some immunology and some physiology. It is expected that the results derived from this project will be relevant to the better understanding of the insulin gene regulation. In addition, the following proposal should also be pertinent in elucidating a more precise hypothesis for the regulation of gene expression during differentiation, development and cancer metastasis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017379-09
Application #
3314373
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1983-02-01
Project End
1995-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming et al. (2015) Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure. Nat Commun 6:8245
Tang, Ke; Rubenstein, John L R; Tsai, Sophia Y et al. (2012) COUP-TFII controls amygdala patterning by regulating neuropilin expression. Development 139:1630-9
Lin, Fu-Jung; You, Li-Ru; Yu, Cheng-Tai et al. (2012) Endocardial cushion morphogenesis and coronary vessel development require chicken ovalbumin upstream promoter-transcription factor II. Arterioscler Thromb Vasc Biol 32:e135-46
Yu, Cheng-Tai; Tang, Ke; Suh, Jae Mi et al. (2012) COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival. Development 139:2330-9
Lin, Fu-Jung; Qin, Jun; Tang, Ke et al. (2011) Coup d'Etat: an orphan takes control. Endocr Rev 32:404-21
Xie, Xin; Qin, Jun; Lin, Sue-Hwa et al. (2011) Nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) modulates mesenchymal cell commitment and differentiation. Proc Natl Acad Sci U S A 108:14843-8
Qin, Jun; Chen, Xinpu; Xie, Xin et al. (2010) COUP-TFII regulates tumor growth and metastasis by modulating tumor angiogenesis. Proc Natl Acad Sci U S A 107:3687-92
Lin, Fu-Jung; Chen, Xinpu; Qin, Jun et al. (2010) Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development. J Clin Invest 120:1694-707
Tang, Ke; Xie, Xin; Park, Joo-In et al. (2010) COUP-TFs regulate eye development by controlling factors essential for optic vesicle morphogenesis. Development 137:725-34
Lee, Dong-Kee; Kurihara, Isao; Jeong, Jae-Wook et al. (2010) Suppression of ERalpha activity by COUP-TFII is essential for successful implantation and decidualization. Mol Endocrinol 24:930-40

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