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Molecular and Cellular Biology, November 2008, p. 6568-6579, Vol. 28, No. 21
0270-7306/08/$08.00+0     doi:10.1128/MCB.02211-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Transcription Factor COUP-TFII Is Negatively Regulated by Insulin and Glucose via Foxo1- and ChREBP-Controlled Pathways{triangledown}

Anaïs Perilhou,1,2 Cécile Tourrel-Cuzin,1,2,{dagger} Ilham Kharroubi,1,2 Carole Henique,1,2 Véronique Fauveau,1,2 Tadahiro Kitamura,3 Christophe Magnan,4 Catherine Postic,1,2 Carina Prip-Buus,1,2 and Mireille Vasseur-Cognet1,2*

Department of Endocrinology, Metabolism, and Cancer, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France,1 Inserm U567, Paris, France,2 Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan,3 Université Paris-Diderot, CNRS UMR 7059, Paris, France4

Received 13 December 2007/ Returned for modification 1 February 2008/ Accepted 16 August 2008

COUP-TFII has an important role in regulating metabolism in vivo. We showed this previously by deleting COUP-TFII from pancreatic beta cells in heterozygous mutant mice, which led to abnormal insulin secretion. Here, we report that COUP-TFII expression is reduced in the pancreas and liver of mice refed with a carbohydrate-rich diet and in the pancreas and liver of hyperinsulinemic and hyperglycemic mice. In pancreatic beta cells, COUP-TFII gene expression is repressed by secreted insulin in response to glucose through Foxo1 signaling. Ex vivo COUP-TFII reduces insulin production and secretion. Our results suggest that beta cell insulin secretion is under the control of an autocrine positive feedback loop by alleviating COUP-TFII repression. In hepatocytes, both insulin, through Foxo1, and high glucose concentrations repress COUP-TFII expression. We demonstrate that this negative glucose effect involves ChREBP expression. We propose that COUP-TFII acts in a coordinate fashion to control insulin secretion and glucose metabolism.

* Corresponding author. Mailing address: Inserm U567, 24 Rue du Faubourg Saint Jacques, Paris, France. Phone: (33) 1 44 41 24 20. Fax: (33) 1 44 41 24 21. E-mail: mireille.vasseur{at}inserm.fr

{triangledown} Published ahead of print on 2 September 2008.

{dagger} Present address: Université Paris-Diderot, CNRS UMR 7059, Paris, France.

Molecular and Cellular Biology, November 2008, p. 6568-6579, Vol. 28, No. 21
0270-7306/08/$08.00+0     doi:10.1128/MCB.02211-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sirek, A. S., Liu, L., Naples, M., Adeli, K., Ng, D. S., Jin, T. (2009). Insulin Stimulates the Expression of Carbohydrate Response Element Binding Protein (ChREBP) by Attenuating the Repressive Effect of Pit-1, Oct-1/Oct-2, and Unc-86 Homeodomain Protein Octamer Transcription Factor-1. Endocrinology 150: 3483-3492 [Abstract] [Full Text]  
  • Aerbajinai, W., Zhu, J., Kumkhaek, C., Chin, K., Rodgers, G. P. (2009). SCF induces {gamma}-globin gene expression by regulating downstream transcription factor COUP-TFII. Blood 114: 187-194 [Abstract] [Full Text]  


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