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However, some of these observations were challenged by other studies. To help address the controversy, we took advantage of zebrafish as a model to perform this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>First, we performed a small\u2010molecule screening for artemether and its skeleton analogues. Second, we used the Cre\u2010LoxP system for lineage tracing to indicate the conversion of alpha cells into beta cells <jats:italic>in vivo<\/jats:italic>. The stable transgenic ins2:eGFP \u03b1TC1\u20106\u2010cell line was used for evaluation of alpha\u2010cell transdifferentiation <jats:italic>in vitro<\/jats:italic>. We further used multiple zebrafish transgenic and mutation lines to demonstrate beta\u2010cell differentiation, beta\u2010cell ablation and alpha\u2010cell hyperplasia in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We showed that artemether and another sesquiterpene, aspterric acid, induced alpha\u2010cell transdifferentiation into beta cells, both in zebrafish as well as using \u03b1TC1\u20106 cells. Furthermore, these two compounds also converted alpha cells into beta cells when beta cells were lost or alpha cells were hyperplastic in zebrafish. Unlike the previous report, the conversion of alpha cells to beta cells was mediated by increasing <jats:italic>Pax4<\/jats:italic> expression, but not suppression of <jats:italic>Arx<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our data suggest that in zebrafish and \u03b1TC1\u20106 cells, both artemether and aspterric acid induce alpha\u2010cell transdifferentiation. Our data, along with those of Li et al. (2017), suggested that artemether and aspterric acid were able to induce alpha\u2010cell transdifferentiation, at least in zebrafish and \u03b1TC1\u20106 cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15769","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T21:56:20Z","timestamp":1638827780000},"page":"1962-1977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Artemether and aspterric acid induce pancreatic alpha cells to transdifferentiate into beta cells in zebrafish"],"prefix":"10.1111","volume":"179","author":[{"given":"Jianxin","family":"Jia","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen China"},{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Kang","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen China"},{"name":"State Key Laboratory of Cellular Stress Biology, School of Life Sciences Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology Xiang'an Hospital of Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence Susan","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity Cardiff University School of Medicine  Cardiff UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingkun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1217-2929","authenticated-orcid":false,"given":"Mingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences Xiamen University  Xiamen China"},{"name":"Department of Otolaryngology Head and Neck Surgery, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"issue":"787","key":"e_1_2_12_2_1","first-page":"e783","article-title":"GABA and artesunate do not induce pancreatic \u03b1\u2010to\u2010\u03b2 cell transdifferentiation in vivo","volume":"28","author":"Ackermann A. 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