AUTHOR=Wu Wenbin , Xia Qingsong , Guo Yujin , Wang Hongzhan , Dong Hui , Lu Fuer , Yuan Fen 

TITLE=Berberine enhances the function of db/db mice islet β cell through GLP-1/GLP-1R/PKA signaling pathway in intestinal L cell and islet α cell

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228722

DOI=10.3389/fphar.2023.1228722

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The evidence on berberine stimulating the secretion of GLP-1 in intestinal L cell has been studied. However, few research has explored its role on generating GLP-1 of islet α cell. Our experiment aims to clarify the mechanism of berberine promoting the secretion of GLP-1 in intestinal L cell and islet α cell, activating GLP-1R and its downstream molecules through endocrine and paracrine ways, thus improving the function of islet β cell and treating T2DM.</p><p><bold>Methods:</bold> After confirming that berberine can lower blood glucose and improve insulin resistance in db/db mice, the identity maintenance, proliferation and apoptosis of islet cells were detected by immunohistochemistry and immunofluorescence. Then, the activation of berberine on GLP-1/GLP-1R/PKA signaling pathway was evaluated by Elisa, Western blot and PCR. Finally, this mechanism was verified by <italic>in vitro</italic> experiments on Min6 cells, STC-1 cells and aTC1/6 cells.</p><p><bold>Results:</bold> Berberine ameliorates glucose metabolism in db/db mice. Additionally, it also increases the number and enhances the function of islet β cell. This process is closely related to improve the secretion of intestinal L cell and islet α cell, activate GLP-1R/PKA signaling pathway through autocrine and paracrine, and increase the expression of its related molecule such as GLP-1, GLP-1R, PC1/3, PC2, PKA, Pdx1. <italic>In vitro</italic>, the phenomenon that berberine enhanced the GLP-1/GLP-1R/PKA signal pathway had also been observed, which confirmed the results of animal experiments.</p><p><bold>Conclusion:</bold> Berberine can maintain the identity and normal function of islet β cell, and its mechanism is related to the activation of GLP-1/GLP-1R/PKA signal pathway in intestinal L cell and islet α cell.</p>