Gfi1 Loss Protects against Two Models of Induced Diabetes

<b>Background:</b> 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 ac...

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Autores principales:	Tiziana Napolitano, Fabio Avolio, Serena Silvano, Sara Forcisi, Anja Pfeifer, Andhira Vieira, Sergi Navarro-Sanz, Marika Elsa Friano, Chaïma Ayachi, Anna Garrido-Utrilla, Josipa Atlija, Biljana Hadzic, Jérôme Becam, Anette Sousa-De-Veiga, Magali Dodille Plaisant, Shruti Balaji, Didier F. Pisani, Magali Mondin, Philippe Schmitt-Kopplin, Ez-Zoubir Amri, Patrick Collombat
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pancreas development amylase ghrelin mouse model high-fat diet Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6dfa825751eb42d887fe5a34c8b254f2
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spelling	oai:doaj.org-article:6dfa825751eb42d887fe5a34c8b254f22021-11-25T17:07:18ZGfi1 Loss Protects against Two Models of Induced Diabetes10.3390/cells101128052073-4409https://doaj.org/article/6dfa825751eb42d887fe5a34c8b254f22021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2805https://doaj.org/toc/2073-4409<b>Background:</b> 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. <b>Methods:</b> In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for <i>Gfi1</i> specifically in the pancreas. <i>Gfi1</i> 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 <i>Gfi1</i>-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. <b>Results:</b> Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic <i>amylase</i> expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, <i>Gfi1</i>-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, <i>Gfi1</i> 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. <b>Conclusions:</b> 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.Tiziana NapolitanoFabio AvolioSerena SilvanoSara ForcisiAnja PfeiferAndhira VieiraSergi Navarro-SanzMarika Elsa FrianoChaïma AyachiAnna Garrido-UtrillaJosipa AtlijaBiljana HadzicJérôme BecamAnette Sousa-De-VeigaMagali Dodille PlaisantShruti BalajiDidier F. PisaniMagali MondinPhilippe Schmitt-KopplinEz-Zoubir AmriPatrick CollombatMDPI AGarticlepancreas developmentamylaseghrelinmouse modelhigh-fat dietBiology (General)QH301-705.5ENCells, Vol 10, Iss 2805, p 2805 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreas development amylase ghrelin mouse model high-fat diet Biology (General) QH301-705.5
spellingShingle	pancreas development amylase ghrelin mouse model high-fat diet Biology (General) QH301-705.5 Tiziana Napolitano Fabio Avolio Serena Silvano Sara Forcisi Anja Pfeifer Andhira Vieira Sergi Navarro-Sanz Marika Elsa Friano Chaïma Ayachi Anna Garrido-Utrilla Josipa Atlija Biljana Hadzic Jérôme Becam Anette Sousa-De-Veiga Magali Dodille Plaisant Shruti Balaji Didier F. Pisani Magali Mondin Philippe Schmitt-Kopplin Ez-Zoubir Amri Patrick Collombat Gfi1 Loss Protects against Two Models of Induced Diabetes
description	<b>Background:</b> 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. <b>Methods:</b> In order to gain further insight into the function of this factor in the pancreas, we generated animals deficient for <i>Gfi1</i> specifically in the pancreas. <i>Gfi1</i> 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 <i>Gfi1</i>-deficient mice with two models of induced hyperglycemia: long-term high-fat/high-sugar feeding and streptozotocin injections. <b>Results:</b> Interestingly, mutant mice did not show any obvious deleterious phenotype. However, in depth analyses demonstrated a significant decrease in pancreatic <i>amylase</i> expression, leading to a diminution in intestinal carbohydrates processing and thus glucose absorption. In fact, <i>Gfi1</i>-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, <i>Gfi1</i> 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. <b>Conclusions:</b> 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.
format	article
author	Tiziana Napolitano Fabio Avolio Serena Silvano Sara Forcisi Anja Pfeifer Andhira Vieira Sergi Navarro-Sanz Marika Elsa Friano Chaïma Ayachi Anna Garrido-Utrilla Josipa Atlija Biljana Hadzic Jérôme Becam Anette Sousa-De-Veiga Magali Dodille Plaisant Shruti Balaji Didier F. Pisani Magali Mondin Philippe Schmitt-Kopplin Ez-Zoubir Amri Patrick Collombat
author_facet	Tiziana Napolitano Fabio Avolio Serena Silvano Sara Forcisi Anja Pfeifer Andhira Vieira Sergi Navarro-Sanz Marika Elsa Friano Chaïma Ayachi Anna Garrido-Utrilla Josipa Atlija Biljana Hadzic Jérôme Becam Anette Sousa-De-Veiga Magali Dodille Plaisant Shruti Balaji Didier F. Pisani Magali Mondin Philippe Schmitt-Kopplin Ez-Zoubir Amri Patrick Collombat
author_sort	Tiziana Napolitano
title	Gfi1 Loss Protects against Two Models of Induced Diabetes
title_short	Gfi1 Loss Protects against Two Models of Induced Diabetes
title_full	Gfi1 Loss Protects against Two Models of Induced Diabetes
title_fullStr	Gfi1 Loss Protects against Two Models of Induced Diabetes
title_full_unstemmed	Gfi1 Loss Protects against Two Models of Induced Diabetes
title_sort	gfi1 loss protects against two models of induced diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6dfa825751eb42d887fe5a34c8b254f2
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Gfi1 Loss Protects against Two Models of Induced Diabetes

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