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Angiotensin (1–7) reverses glucose-induced islet β cell dedifferentiation by Wnt/β-catenin/FoxO1 signalling pathway
Affiliations- Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China
- Department of Endocrinology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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Abstract
Introduction: Recent studies have shown that a decline in islet β cells quality is due to β-cell dedifferentiation, not only β-cell apoptosis. Angiotensin (1–7) [Ang(1-7)] could attenuate high glucose-induced apoptosis and dedifferentiation of pancreatic β cells by combining with MAS receptors. However, the mechanism of such action has not been elucidated. Recent studies have revealed that Wnt/β-catenin and forkhead box transcription factor O1 (FoxO1) are associated with β-cell dedifferentiation. Our study aims to explore whether the effects of Ang(1-7)on islet b cell dedifferentiation are mediated through the Wnt/β-catenin/FoxO1 pathway.
Material and methods: Islet β cells were divided into 6 groups: a control group, a high-glucose group, high glucose with Ang(1-7) group, high-glucose with Ang(1-7) and A779 group, high-glucose with angiotensin(1-7) and CHIR99021 group, and high-glucose with CHIR99021 group. A779 is a kind of MAS receptor antagonist that blocks the action of Ang(1-7), and CHIR99021 is a Wnt pathway activator. The morphology of pancreatic β cells was observed in each group after 48 hours of intervention. β-cell insulin secretory function and expressions of relevant factors were measured.
Results: Compared with the control group, the cell morphology became degraded in the high-glucose group and the capability of insulin secretion was reduced. Meanwhile, the expressions of mature β cells markers [pancreatic and duodenal homeobox 1 (Pdx1) and MAF BZIP transcription factor A (MafA)] were reduced, while the expressions of endocrine progenitor cells makers [octamer-binding transcription factor 4 (Oct4) and Nanog] were increased. The addition of CHIR99021 resulted in profound deep destruction of β cells compared with the high-glucose group. However, such changes were dramatically reversed following the treatment of Ang(1-7). The addition of A779 significantly inhibited the improvement caused by Ang(1-7).
Conclusion: Ang(1-7) can effectively reverse β cell dedifferentiation through Wnt/β-catenin/FoxO1 pathway. It might be a new strategy for preventing and treating diabetes.
Abstract
Introduction: Recent studies have shown that a decline in islet β cells quality is due to β-cell dedifferentiation, not only β-cell apoptosis. Angiotensin (1–7) [Ang(1-7)] could attenuate high glucose-induced apoptosis and dedifferentiation of pancreatic β cells by combining with MAS receptors. However, the mechanism of such action has not been elucidated. Recent studies have revealed that Wnt/β-catenin and forkhead box transcription factor O1 (FoxO1) are associated with β-cell dedifferentiation. Our study aims to explore whether the effects of Ang(1-7)on islet b cell dedifferentiation are mediated through the Wnt/β-catenin/FoxO1 pathway.
Material and methods: Islet β cells were divided into 6 groups: a control group, a high-glucose group, high glucose with Ang(1-7) group, high-glucose with Ang(1-7) and A779 group, high-glucose with angiotensin(1-7) and CHIR99021 group, and high-glucose with CHIR99021 group. A779 is a kind of MAS receptor antagonist that blocks the action of Ang(1-7), and CHIR99021 is a Wnt pathway activator. The morphology of pancreatic β cells was observed in each group after 48 hours of intervention. β-cell insulin secretory function and expressions of relevant factors were measured.
Results: Compared with the control group, the cell morphology became degraded in the high-glucose group and the capability of insulin secretion was reduced. Meanwhile, the expressions of mature β cells markers [pancreatic and duodenal homeobox 1 (Pdx1) and MAF BZIP transcription factor A (MafA)] were reduced, while the expressions of endocrine progenitor cells makers [octamer-binding transcription factor 4 (Oct4) and Nanog] were increased. The addition of CHIR99021 resulted in profound deep destruction of β cells compared with the high-glucose group. However, such changes were dramatically reversed following the treatment of Ang(1-7). The addition of A779 significantly inhibited the improvement caused by Ang(1-7).
Conclusion: Ang(1-7) can effectively reverse β cell dedifferentiation through Wnt/β-catenin/FoxO1 pathway. It might be a new strategy for preventing and treating diabetes.
Keywords
diabetes; dedifferentiation of islet β cells; insulin secretion; angiotensin (1–7); Wnt/β-catenin/FoxO1 pathway
About this articleTitle
Angiotensin (1–7) reverses glucose-induced islet β cell dedifferentiation by Wnt/β-catenin/FoxO1 signalling pathway
Journal
Issue
Article type
Original paper
Pages
544-552
Published online
2023-09-27
Page views
457
Article views/downloads
283
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2023;74(5):544-552.
Keywords
diabetes
dedifferentiation of islet β cells
insulin secretion
angiotensin (1–7)
Wnt/β-catenin/FoxO1 pathway
Authors
Dandan Guo
Junhua He
Hao Guo
Guoning Song
Lina Peng
Min An
Caixia Wang
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