{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:46:39Z","timestamp":1791809199316,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":284,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2023J011776"],"award-info":[{"award-number":["2023J011776"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Progressive pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell injury is a core feature of Type 2 diabetes mellitus (T2DM). Imbalance between macrophage M1 and M2 polarization, driven by chronic inflammation, is a key contributor to this injury. The Keap1\u2010Nrf2\u2010ARE pathway regulates macrophage polarization and inflammatory responses, but whether it affects pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell survival through macrophages is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated a\n                      <jats:italic>Keap1<\/jats:italic>\n                      \u2010knockout THP\u20101 line using CRISPR\u2010Cas9, differentiated the cells into M0 macrophages with PMA, polarized them toward M2 with IL\u20104\/IL\u201013, and cocultured them with MIN6 cells injured by LPS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Keap1<\/jats:italic>\n                      knockout increased M2 polarization efficiency and reduced the nuclear\u2010to\u2010cytoplasmic ratio of NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B p65, with lower IL\u20101\n                      <jats:italic>\u03b2<\/jats:italic>\n                      and TNF\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      mRNA expression. After coculture with LPS\u2010injured MIN6 cells, the Keap1\u2010KO\u2010M2 group showed higher MIN6 viability and less apoptosis. The antiapoptotic protein Bcl\u20102 rose, whereas the proapoptotic factors Bax and cleaved\u2010caspase3 declined; MDA content fell, whereas HO\u20101 and SOD levels climbed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings indicate that\n                      <jats:italic>Keap1<\/jats:italic>\n                      deficiency attenuates LPS\u2010induced pancreatic\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010cell injury by increasing macrophage M2 polarization efficiency and expanding the M2 population.\n                    <\/jats:p>\n                  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Affiliated to Fujian Medical University  Quanzhou Fujian China  fjmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3487-9905","authenticated-orcid":false,"given":"Xiaoyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Quanzhou First Hospital Affiliated to Fujian Medical University  Quanzhou Fujian China  fjmu.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Su","sequence":"additional","affiliation":[{"name":"The 910th Hospital of the Joint Logistics Support Force of the Chinese People\u2032s Liberation Army  Quanzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Hong","sequence":"additional","affiliation":[{"name":"Quanzhou First Hospital Affiliated to Fujian Medical University  Quanzhou Fujian China  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