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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MDPI AG
2021-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/2805 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:37:22Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:22Z |
| publishDate | 2021-10-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-6dfa825751eb42d887fe5a34c8b254f22023-11-22T22:47:01ZengMDPI AGCells2073-44092021-10-011011280510.3390/cells10112805Gfi1 Loss Protects against Two Models of Induced DiabetesTiziana Napolitano0Fabio Avolio1Serena Silvano2Sara Forcisi3Anja Pfeifer4Andhira Vieira5Sergi Navarro-Sanz6Marika Elsa Friano7Chaïma Ayachi8Anna Garrido-Utrilla9Josipa Atlija10Biljana Hadzic11Jérôme Becam12Anette Sousa-De-Veiga13Magali Dodille Plaisant14Shruti Balaji15Didier F. Pisani16Magali Mondin17Philippe Schmitt-Kopplin18Ez-Zoubir Amri19Patrick Collombat20Faculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceResearch Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environment Health, 85764 Neuherberg, GermanyFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceCIRAD, UMR AGAP, 34398 Montpellier, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceTAAM, CNRS, UPS 44, 45100 Orleans, FrancePediatric Oncology & Hematology Department, Centre Hospitalier Universitaire de Nice, Hopital Archet 2, 06202 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FrancePlantaCorp GmbH, 20097 Hamburg, GermanyMedicine Faculty, Université Côte d’Azur, CNRS, LP2M, 06003 Nice, FrancePôle Imagerie Photonique, Bordeaux Imaging Center, Université de Bordeaux, UMS 3420 CNRS-US4 Inserm, 33076 Bordeaux, FranceResearch Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, German Research Center for Environment Health, 85764 Neuherberg, GermanyFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, FranceFaculté des Sciences, Université Côte d’Azur, CNRS, Inserm, iBV, Parc Valrose, 06108 Nice, France<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.https://www.mdpi.com/2073-4409/10/11/2805pancreas developmentamylaseghrelinmouse modelhigh-fat diet |
| spellingShingle | 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 Cells pancreas development amylase ghrelin mouse model high-fat diet |
| title | 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_short | Gfi1 Loss Protects against Two Models of Induced Diabetes |
| title_sort | gfi1 loss protects against two models of induced diabetes |
| topic | pancreas development amylase ghrelin mouse model high-fat diet |
| url | https://www.mdpi.com/2073-4409/10/11/2805 |
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