期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.605110
关键词
pancreatic α -cell; pancreatic β -cell; regeneration; betacellulin; ErbB receptor
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015R1D1A1A01060232, NRF-2018R1D1A1B07048223]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1135]
Betacellulin (BTC) has been shown to promote alpha-cell proliferation by interacting with ErbB-3 and ErbB-4 receptors, suggesting that these increased alpha-cells may serve as a potential source of new beta-cells.
Betacellulin (BTC), an epidermal growth factor family, is known to promote beta-cell regeneration. Recently, pancreatic alpha-cells have been highlighted as a source of new beta-cells. We investigated the effect of BTC on alpha-cells. Insulin+glucagon+ double stained bihormonal cell levels and pancreatic and duodenal homeobox-1 expression were increased in mice treated with recombinant adenovirus-expressing BTC (rAd-BTC) and beta-cell-ablated islet cells treated with BTC. In the islets of rAd-BTC-treated mice, both BrdU+glucagon+ and BrdU+insulin+ cell levels were significantly increased, with BrdU+glucagon+ cells showing the greater increase. Treatment of alpha TC1-9 cells with BTC significantly increased proliferation and cyclin D2 expression. BTC induced phosphorylation of ErbB receptors in alpha TC1-9 cells. The proliferative effect of BTC was mediated by ErbB-3 or ErbB-4 receptor kinase. BTC increased phosphorylation of ERK1/2, AKT, and mTOR and PC1/3 expression and GLP-1 production in alpha-cells, but BTC-induced proliferation was not changed by the GLP-1 receptor antagonist, exendin-9. We suggest that BTC has a direct role in alpha-cell proliferation via interaction with ErbB-3 and ErbB-4 receptors, and these increased alpha-cells might be a source of new beta-cells.
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