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Article Dans Une Revue Cells Année : 2021

Gfi1 Loss Protects against Two Models of Induced Diabetes

Tiziana Napolitano
  • Fonction : Auteur
Fabio Avolio
  • Fonction : Auteur
Serena Silvano
  • Fonction : Auteur
Sara Forcisi
Anja Pfeifer
  • Fonction : Auteur
Andhira Vieira
  • Fonction : Auteur
Sergi Navarro-Sanz
  • Fonction : Auteur
Marika Elsa Friano
  • Fonction : Auteur
Chaïma Ayachi
  • Fonction : Auteur
Anna Garrido-Utrilla
Josipa Atlija
  • Fonction : Auteur
Biljana Hadzic
  • Fonction : Auteur
Jérôme Becam
  • Fonction : Auteur
Anette Sousa-De-Veiga
  • Fonction : Auteur
Magali Dodille Plaisant
Shruti Balaji
  • Fonction : Auteur
Didier Pisani
Magali Mondin
Philippe Schmitt-Kopplin
Ez-Zoubir Amri
Patrick Collombat
  • Fonction : Auteur

Résumé

Background: Although several approaches have revealed much about individual factors that regulate pancreatic development, we have yet to fully understand their complicated interplay during pancreas morphogenesis. Gfi1 is transcription factor specifically expressed in pancreatic acinar cells, whose role in pancreas cells fate identity and specification is still elusive. Methods: In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for Gfi1 specifically in the pancreas. Gfi1 conditional knockout animals were phenotypically characterized by immunohistochemistry, RT-qPCR, and RNA scope. To assess the role of Gfi1 in the pathogenesis of diabetes, we challenged Gfi1-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. Results: Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic amylase expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, Gfi1-deficient mice were found resistant to diet-induced hyperglycemia, appearing normoglycemic even after long-term high-fat/high-sugar diet. Another feature observed in mutant acinar cells was the misexpression of ghrelin, a hormone previously suggested to exhibit anti-apoptotic effects on β-cells in vitro. Impressively, Gfi1 mutant mice were found to be resistant to the cytotoxic and diabetogenic effects of high-dose streptozotocin administrations, displaying a negligible loss of β-cells and an imperturbable normoglycemia. Conclusions: Together, these results demonstrate that Gfi1 could turn to be extremely valuable for the development of new therapies and could thus open new research avenues in the context of diabetes research.
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hal-03472645 , version 1 (09-12-2021)

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Tiziana Napolitano, Fabio Avolio, Serena Silvano, Sara Forcisi, Anja Pfeifer, et al.. Gfi1 Loss Protects against Two Models of Induced Diabetes. Cells, 2021, 10 (11), pp.2805. ⟨10.3390/cells10112805⟩. ⟨hal-03472645⟩
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