Angiotensin (1-7) reverses glucose-induced islet β cell dedifferentiation by Wnt/β-catenin/FoxO1 signalling pathway

Introduction: Recent studies have shown that a decline in islet beta cells quality is due to beta-cell dedifferentiation, not only beta-cell Apoptosis. Angiotensin (1-7) [Ang(1-7)] could attenuate high glucose-induced Apoptosis and dedifferentiation of pancreatic beta cells by combining with MAS receptors. However, the mechanism of such action has not been elucidated. Recent studies have revealed that Wnt/beta-catenin and forkhead box transcription factor O1 (FoxO1) are associated with beta-cell dedifferentiation. Our study aims to explore whether the effects of Ang(1-7)on islet b cell dedifferentiation are mediated through the Wnt/beta-catenin/FoxO1 pathway.Material and methods: Islet beta 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 beta cells was observed in each group after 48 hours of intervention. beta-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 beta 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 beta 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 beta cell dedifferentiation through Wnt/beta-catenin/FoxO1 pathway. It might be a new strategy for preventing and treating diabetes.

Automated summary

Recent studies have found that Ang(1-7) can reverse beta-cell dedifferentiation through the Wnt/beta-catenin/FoxO1 pathway, which may be a novel strategy for preventing and treating diabetes.