title: The transcription factor COUP-TFII is negatively regulated by insulin and glucose via Foxo1- and ChREBP-controlled pathways.
abstract: 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.
authors.affiliation: Department of Endocrinology, Metabolism, and Cancer, Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Perilhou
authors.forename: Cécile
authors.initials: C
authors.lastname: Tourrel-Cuzin
authors.forename: Ilham
authors.initials: I
authors.lastname: Kharroubi
authors.forename: Carole
authors.initials: C
authors.lastname: Henique
authors.forename: Véronique
authors.initials: V
authors.lastname: Fauveau
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.forename: Catherine
authors.initials: C
authors.lastname: Postic
authors.forename: Carina
authors.initials: C
authors.lastname: Prip-Buus
authors.forename: Mireille
authors.initials: M
authors.lastname: Vasseur-Cognet