Request for Funding

Medical Student Research Fellowship for Summer 2004

Mentor: Kosaku Uyeda
Department: Biochemistry
Room number:VA bldg3 Rm115
Mail Code: 9038/VA
Phone number: 214-857-0318
E-mail:kuyeda6400@aol.com
Project title: Carbohydrate regulation of hepatic gene expression

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic research

Brief Description of Project: We have isolated and identified carbohydrate response element binding protein (ChREBP) which is required for basal and carbohydrate-induced expression of several liver enzymes essential for coordinated control of glucose metabolism and fat synthesis. We have prepared both ChREBP knockout mice and intercrossed with ob/ob mice and currently investigating their phenotypes. We are also investigating structure and function of ChREBP in vivo and in vitro.

Previous Research Activities or Publications with Medical Students (selected):

Yamashita, H.,Takenoshita, M., Sakurai, M., Bruick, R.K., Henzel, W.J., Shillinglaw, W., Arnot, D., and Uyeda, K.,(2001) A Glucose-Responsive Transcription Factor that regulates Carbohydrate Metabolism in the liver. Proc Natl. Acad. Sci. 98, 9116-9121.
Kawaguchi, T., Takenoshita, M., Kabashima, T., and Uyeda, K. (2001) Glucose and cAMP Regulate L-type Pyruvate Kinase Gene by Phosphorylation/Dephosphorylation of the Carbohydrate Response Element Binding Protein. Proc. Natl..Acad. Sci. 98, 13710 - 13715
Kawaguchi, T., Osatomi, K, Yamashita, H., Kabashima, T., and Uyeda, K. (2002) Mechanism of Fatty Acids "Sparing Effect" on Glucose-induced Transcription: Regulation of Carbohydrate Response Element Binding Protein by AMP-Activated Protein Kinase. J. Biol. Chem 277, 3829- 3835.
Uyeda, K., Yamashita, H., and Kawaguchi, K., (2002) Commentary. Carbohydrate Responsive Element Binding Protein (ChREBP): A key Regulator of Glucose Metabolism and Fat Storage. Biochem. Pharmacol. 7243, 1 - 6.
Lee, Y.H., Li , Y., Uyeda, K. and Hasemann C. A.(2003) Tissue-specific Structure/Function Deifferentiation of the Liver isoform of 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase. J. Biol. Chem. 278, 523-530.
Kabashima, T., Kawaguchi, T., and Uyeda, K. (2003) Xylulose-5-phosaphate Activated Protein Phosphatase is Mechanism of Hepatic Glucose-induced Lipogenesis. Proc. Natl. Acad. Sci. USA 100, 5107-5112.
Jin, E. S., Uyeda, K., Kawaguchi, T., Burgess, S., Malloy, C. R., and Sherry, A. D. (2003) Increased hepatic fructose 2,6-bisphosphate after an oral glucose load does not affect gluconeogenesis. J. Biol Chem. 278, 28427-28433.
Iizuka, K., Bruick, R.K., Liang, G., Horton, J.D., and Uyeda, K. (2004) Deficiency of carbohydrate response element binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc. Natl. Acad. Sci. USA.( in press).

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