|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 20, 17564-17570, May 17, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Division of Clinical Biochemistry, Department of Internal
Medicine, University Medical Center, CH-1211 Geneva
4, Switzerland
The transcription factor Foxa2 is implicated in
blood glucose homeostasis. Conditional expression of Foxa2 or its
dominant-negative mutant DN-Foxa2 in INS-1 cells reveals that Foxa2
regulates the expression of genes important for glucose sensing in
pancreatic
Foxa2 (HNF3
) Controls Multiple Genes Implicated in
Metabolism-Secretion Coupling of Glucose-induced Insulin Release*
,
-cells. Overexpression of Foxa2 results in blunted
glucose-stimulated insulin secretion, whereas induction of DN-Foxa2
causes a left shift of glucose-induced insulin release. The mRNA
levels of GLUT2 and glucokinase are drastically decreased after
induction of Foxa2. In contrast, loss of Foxa2 function leads to
up-regulation of hexokinase (HK) I and II and glucokinase (HK-IV)
mRNA expression. The glucokinase and the low Km
hexokinase activities as well as glycolysis are increased
proportionally. In addition, induction of DN-Foxa2 also reduces the
expression of -cell KATP channel subunits Sur1 and
Kir6.2 by 70%. Furthermore, in contrast to previous reports, induction
of Foxa2 causes pronounced decreases in the HNF4
and HNF1
mRNA levels. Foxa2 fails to regulate the expression of Pdx1
transcripts. The expression of insulin and islet amyloid
polypeptide is markedly suppressed after induction of Foxa2,
while the glucagon mRNA levels are significantly increased. Conversely, Foxa2 is required for glucagon expression in these INS-1-derived cells. These results suggest that Foxa2 is a vital transcription factor evolved to control the expression of genes essential for maintaining -cell glucose sensing and glucose homeostasis.
*
This work was supported by the Swiss National Science
Foundation Grant 32-49755.96.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Division
de Biochimie Clinique et de Diabétologie Expérimentale,
Dépt. de Médecine Interne, Center Médical
Universitaire, CH-1211 Geneva 4, Switzerland. Tel.: 41-22-702-5570;
Fax: 41-22-702-5543; E-mail: Haiyan.Wang@medicine. unige.ch.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Miura, Y. Tomaru, M. Nakanishi, S. Kondo, Y. Hayashizaki, and M. Suzuki Identification of DNA regions and a set of transcriptional regulatory factors involved in transcriptional regulation of several human liver-enriched transcription factor genes Nucleic Acids Res., February 1, 2009; 37(3): 778 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Qian, H. Wang, X. Men, W. Zhang, H. Cai, S. Xu, Y. Xu, L. Ye, C. B Wollheim, and J. Lou TRIB3 is implicated in glucotoxicity- and oestrogen receptor-stress-induced {beta}-cell apoptosis J. Endocrinol., December 1, 2008; 199(3): 407 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C Martin, B. P Flemming, Y. Wang, J. K Oeser, and R. M O'Brien Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression J. Mol. Endocrinol., November 1, 2008; 41(5): 315 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Philip-Couderc, N. I. Tavares, A. Roatti, R. Lerch, C. Montessuit, and A. J. Baertschi Forkhead Transcription Factors Coordinate Expression of Myocardial KATP Channel Subunits and Energy Metabolism Circ. Res., February 1, 2008; 102(2): e20 - e35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Baroukh, M. A. Ravier, M. K. Loder, E. V. Hill, A. Bounacer, R. Scharfmann, G. A. Rutter, and E. Van Obberghen MicroRNA-124a Regulates Foxa2 Expression and Intracellular Signaling in Pancreatic {beta}-Cell Lines J. Biol. Chem., July 6, 2007; 282(27): 19575 - 19588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Miele, G. A. Raciti, A. Cassese, C. Romano, F. Giacco, F. Oriente, F. Paturzo, F. Andreozzi, A. Zabatta, G. Troncone, et al. PED/PEA-15 Regulates Glucose-Induced Insulin Secretion by Restraining Potassium Channel Expression in Pancreatic {beta}-Cells Diabetes, March 1, 2007; 56(3): 622 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. McKinnon, M. A. Ravier, and G. A. Rutter FoxO1 Is Required for the Regulation of Preproglucagon Gene Expression by Insulin in Pancreatic {alpha}TC1-9 Cells J. Biol. Chem., December 22, 2006; 281(51): 39358 - 39369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Parton, P. J. McMillen, Y. Shen, E. Docherty, E. Sharpe, F. Diraison, C. P. Briscoe, and G. A. Rutter Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E982 - E994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I Giurgea, D Sanlaville, J-C Fournet, C Sempoux, C Bellanne-Chantelot, G Touati, L Hubert, M-S Groos, F Brunelle, J Rahier, et al. Congenital hyperinsulinism and mosaic abnormalities of the ploidy J. Med. Genet., March 1, 2006; 43(3): 248 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hashimoto, T. Nakamura, H. Maegawa, Y. Nishio, K. Egawa, and A. Kashiwagi Regulation of ATP-sensitive Potassium Channel Subunit Kir6.2 Expression in Rat Intestinal Insulin-producing Progenitor Cells J. Biol. Chem., January 21, 2005; 280(3): 1893 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Flock, X. Cao, and D. J. Drucker Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells Endocrinology, January 1, 2005; 146(1): 441 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Thomas, S. Senkel, S. Erdmann, T. Arndt, G. Turan, L. Klein-Hitpass, and G. U. Ryffel Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4{alpha} and HNF1{beta} in a pancreatic {beta}-cell line Nucleic Acids Res., November 1, 2004; 32(19): e150 - e150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. DUNNE, K. E. COSGROVE, R. M. SHEPHERD, A. AYNSLEY-GREEN, and K. J. LINDLEY Hyperinsulinism in Infancy: From Basic Science to Clinical Disease Physiol Rev, January 1, 2004; 84(1): 239 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, K. Hagenfeldt-Johansson, L. A. Otten, B. R. Gauthier, P. L. Herrera, and C. B. Wollheim Experimental Models of Transcription Factor-Associated Maturity-Onset Diabetes of the Young Diabetes, December 1, 2002; 51(90003): S333 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hu, J. E. Ippolito, E. M. Garabedian, P. A. Humphrey, and J. I. Gordon Molecular Characterization of a Metastatic Neuroendocrine Cell Cancer Arising in the Prostates of Transgenic Mice J. Biol. Chem., November 8, 2002; 277(46): 44462 - 44474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Lee, N. J. Sund, M. Z. Vatamaniuk, F. M. Matschinsky, D. A. Stoffers, and K. H. Kaestner Foxa2 Controls Pdx1 Gene Expression in Pancreatic {beta}-Cells In Vivo Diabetes, August 1, 2002; 51(8): 2546 - 2551. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |