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Article

Gfi1 Loss Protects against Two Models of Induced Diabetes

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Faculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, France
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Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark
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Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environment Health, 85764 Neuherberg, Germany
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German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
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CIRAD, UMR AGAP, 34398 Montpellier, France
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TAAM, CNRS, UPS 44, 45100 Orleans, France
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Pediatric Oncology & Hematology Department, Centre Hospitalier Universitaire de Nice, Hopital Archet 2, 06202 Nice, France
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PlantaCorp GmbH, 20097 Hamburg, Germany
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Medicine Faculty, Université Côte d’Azur, CNRS, LP2M, 06003 Nice, France
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Pôle Imagerie Photonique, Bordeaux Imaging Center, Université de Bordeaux, UMS 3420 CNRS-US4 Inserm, 33076 Bordeaux, France
*
Author to whom correspondence should be addressed.
Academic Editor: Jean Sébastien Annicotte
Cells 2021, 10(11), 2805; https://doi.org/10.3390/cells10112805
Received: 8 September 2021 / Revised: 7 October 2021 / Accepted: 14 October 2021 / Published: 20 October 2021
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
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. View Full-Text
Keywords: pancreas development; amylase; ghrelin; mouse model; high-fat diet pancreas development; amylase; ghrelin; mouse model; high-fat diet
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MDPI and ACS Style

Napolitano, T.; Avolio, F.; Silvano, S.; Forcisi, S.; Pfeifer, A.; Vieira, A.; Navarro-Sanz, S.; Friano, M.E.; Ayachi, C.; Garrido-Utrilla, A.; Atlija, J.; Hadzic, B.; Becam, J.; Sousa-De-Veiga, A.; Plaisant, M.D.; Balaji, S.; Pisani, D.F.; Mondin, M.; Schmitt-Kopplin, P.; Amri, E.-Z.; Collombat, P. Gfi1 Loss Protects against Two Models of Induced Diabetes. Cells 2021, 10, 2805. https://doi.org/10.3390/cells10112805

AMA Style

Napolitano T, Avolio F, Silvano S, Forcisi S, Pfeifer A, Vieira A, Navarro-Sanz S, Friano ME, Ayachi C, Garrido-Utrilla A, Atlija J, Hadzic B, Becam J, Sousa-De-Veiga A, Plaisant MD, Balaji S, Pisani DF, Mondin M, Schmitt-Kopplin P, Amri E-Z, Collombat P. Gfi1 Loss Protects against Two Models of Induced Diabetes. Cells. 2021; 10(11):2805. https://doi.org/10.3390/cells10112805

Chicago/Turabian Style

Napolitano, Tiziana, Fabio Avolio, Serena Silvano, Sara Forcisi, Anja Pfeifer, Andhira Vieira, Sergi Navarro-Sanz, Marika E. Friano, Chaïma Ayachi, Anna Garrido-Utrilla, Josipa Atlija, Biljana Hadzic, Jérôme Becam, Anette Sousa-De-Veiga, Magali D. Plaisant, Shruti Balaji, Didier F. Pisani, Magali Mondin, Philippe Schmitt-Kopplin, Ez-Zoubir Amri, and Patrick Collombat. 2021. "Gfi1 Loss Protects against Two Models of Induced Diabetes" Cells 10, no. 11: 2805. https://doi.org/10.3390/cells10112805

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