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We previously demonstrated that macrophage-derived interferon (IFN) \u03b2 induced X-linked inhibitor of apoptosis\u2013associated factor 1 (XAF1) expression in \u03b2-cells and accelerated \u03b2-cell apoptosis in vitro. Here, we explored the effects of XAF1 on \u03b2-cell function and progression of diabetes in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Pancreatic \u03b2-cell-selective XAF1 overexpressing (<jats:italic>Xaf1<\/jats:italic> Tg) mice were generated. <jats:italic>Xaf1<\/jats:italic> Tg mice and their wild-type (WT) littermates were fed either a normal diet or a 40% or 60% high-fat diet (HFD). The effects of \u03b2-cell XAF1 on \u03b2-cell apoptosis and exacerbation of diabetes were investigated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Palmitic acid induced IFN\u03b2 expression in macrophages, and HFD intake promoted macrophage infiltration in pancreatic islets, both of which cooperatively upregulated XAF1 expression in mouse islets. Furthermore, HFD-fed <jats:italic>Xaf1<\/jats:italic> Tg mice demonstrated increased \u03b2-cell apoptosis, lowered insulin expression, and impaired glucose tolerance compared with WT mice fed the same diet. These effects were more pronounced in the 60%HFD group than in the 40%HFD group.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Pancreatic \u03b2-cell XAF1 expression was enhanced via HFD-induced, macrophage-derived IFN\u03b2, which promoted \u03b2-cell apoptosis and led to a reduction in insulin secretion and progression of diabetes. To our knowledge, this is the first report to demonstrate an association between pancreatic \u03b2-cell XAF1 overexpression and exacerbation of diabetes, thus providing insight into the mechanism of \u03b2-cell mass reduction in diabetes.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00592-022-01930-y","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T08:03:36Z","timestamp":1657699416000},"page":"1275-1286","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["XAF1 overexpression exacerbates diabetes by promoting pancreatic \u03b2-cell apoptosis"],"prefix":"10.1007","volume":"59","author":[{"given":"Yuki","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-346X","authenticated-orcid":false,"given":"Misaki","family":"Iwashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Shinjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Zeze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terukazu","family":"Sanui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoichiro","family":"Asano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusanori","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"issue":"7","key":"1930_CR1","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.tips.2015.04.014","volume":"36","author":"M Fasshauer","year":"2015","unstructured":"Fasshauer M, Bl\u00fcher M (2015) Adipokines in health and disease. 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