Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors
The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease pro...
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3698 |
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| author | Luiza Ghila Thomas Aga Legøy Andreas Frøslev Mathisen Shadab Abadpour Joao A. Paulo Hanne Scholz Helge Ræder Simona Chera |
| author_facet | Luiza Ghila Thomas Aga Legøy Andreas Frøslev Mathisen Shadab Abadpour Joao A. Paulo Hanne Scholz Helge Ræder Simona Chera |
| author_sort | Luiza Ghila |
| collection | DOAJ |
| description | The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature. |
| first_indexed | 2024-03-10T12:40:05Z |
| format | Article |
| id | doaj.art-e88652becfd64a1ebb6a3b88592a862b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:40:05Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e88652becfd64a1ebb6a3b88592a862b2023-11-21T13:59:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01227369810.3390/ijms22073698Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic ProgenitorsLuiza Ghila0Thomas Aga Legøy1Andreas Frøslev Mathisen2Shadab Abadpour3Joao A. Paulo4Hanne Scholz5Helge Ræder6Simona Chera7Center for Diabetes Research, Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, NorwayCenter for Diabetes Research, Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, NorwayCenter for Diabetes Research, Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, NorwayHybrid Technology Hub-Centre of Excellence, Faculty of Medicine, University of Oslo, 0318 Oslo, NorwayDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USAHybrid Technology Hub-Centre of Excellence, Faculty of Medicine, University of Oslo, 0318 Oslo, NorwayCenter for Diabetes Research, Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, NorwayCenter for Diabetes Research, Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, NorwayThe past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature.https://www.mdpi.com/1422-0067/22/7/3698cell identitycell fatein vitro differentiationpancreatic endocrine progenitorshiPSCsignaling pathway analyses |
| spellingShingle | Luiza Ghila Thomas Aga Legøy Andreas Frøslev Mathisen Shadab Abadpour Joao A. Paulo Hanne Scholz Helge Ræder Simona Chera Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors International Journal of Molecular Sciences cell identity cell fate in vitro differentiation pancreatic endocrine progenitors hiPSC signaling pathway analyses |
| title | Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors |
| title_full | Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors |
| title_fullStr | Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors |
| title_full_unstemmed | Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors |
| title_short | Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors |
| title_sort | chronically elevated exogenous glucose elicits antipodal effects on the proteome signature of differentiating human ipsc derived pancreatic progenitors |
| topic | cell identity cell fate in vitro differentiation pancreatic endocrine progenitors hiPSC signaling pathway analyses |
| url | https://www.mdpi.com/1422-0067/22/7/3698 |
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