Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4γ: A Critical Role for Enteroendocrine Cell Lineage. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Diabetes Année : 2015

Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4γ: A Critical Role for Enteroendocrine Cell Lineage.

Floriane Baraille
  • Fonction : Auteur
Sami Ayari
  • Fonction : Auteur
Véronique Carrière
  • Fonction : Auteur
Céline Osinski
  • Fonction : Auteur
Kevin Garbin
  • Fonction : Auteur
Bertrand Blondeau
  • Fonction : Auteur
Patricia Serradas
  • Fonction : Auteur
Monique Rousset
  • Fonction : Auteur
Michel Lacasa
  • Fonction : Auteur
Philippe Cardot
  • Fonction : Auteur
Agnès Ribeiro
  • Fonction : Auteur

Résumé

Intestine contributes to energy homeostasis through the absorption, metabolism, and transfer of nutrients to the organism. We demonstrated previously that hepatocyte nuclear receptor-4α (HNF-4α) controls intestinal epithelium homeostasis and intestinal absorption of dietary lipids. HNF-4γ, the other HNF-4 form highly expressed in intestine, is much less studied. In HNF-4γ knockout mice, we detect an exaggerated insulin peak and improvement in glucose tolerance during oral but not intraperitoneal glucose tolerance tests, highlighting the involvement of intestine. Moreover, the enteroendocrine L-type cell lineage is modified, as assessed by the increased expression of transcription factors Isl1, Foxa1/2, and Hnf4a, leading to an increase of both GLP-1–positive cell number and basal and stimulated GLP-1 plasma levels potentiating the glucose-stimulated insulin secretion. Using the GLP-1 antagonist exendin (9-39), we demonstrate a direct effect of GLP-1 on improved glucose tolerance. GLP-1 exerts a trophic effect on pancreatic β-cells, and we report an increase of the β-cell fraction correlated with an augmented number of proliferative islet cells and with resistance to streptozotocin-induced diabetes. In conclusion, the loss of HNF-4γ improves glucose homeostasis through a modulation of the enteroendocrine cell lineage.

Dates et versions

hal-03990038 , version 1 (15-02-2023)

Identifiants

Citer

Floriane Baraille, Sami Ayari, Véronique Carrière, Céline Osinski, Kevin Garbin, et al.. Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4γ: A Critical Role for Enteroendocrine Cell Lineage.. Diabetes, 2015, 64 (8), pp.2744. ⟨10.2337/db14-0993⟩. ⟨hal-03990038⟩
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