{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:47:37Z","timestamp":1793738857000,"version":"4.6.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pancreatic \u03b2-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. \u03b2-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human \u03b2-cells. We show that primary human \u03b2-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of \u03b2-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced \u03b2-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional \u03b2-cell mass in early stages of development of T1D.<\/jats:p>","DOI":"10.3389\/fimmu.2021.690379","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T04:24:36Z","timestamp":1635999876000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":112,"title":["Oxidative Stress Leads to \u03b2-Cell Dysfunction Through Loss of \u03b2-Cell Identity"],"prefix":"10.3389","volume":"12","author":[{"given":"Floris","family":"Leenders","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Groen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"de Graaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marten\u00a0A.","family":"Engelse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton J.","family":"Rabelink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eelco J. 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