{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:17:54Z","timestamp":1787314674431,"version":"build-2736575974"},"reference-count":49,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T00:00:00Z","timestamp":1540166400000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:p>Type 1 diabetes (T1D) is an autoimmune disease where pancreatic \u03b2-cells are destroyed by islet-infiltrating T cells. Although a role for \u03b2-cell defects has been suspected, \u03b2-cell abnormalities are difficult to demonstrate. We show a \u03b2-cell DNA damage response (DDR), presented by activation of the 53BP1 protein and accumulation of p53, in biopsy and autopsy material from patients with recently diagnosed T1D as well as a rat model of human T1D. The \u03b2-cell DDR is more frequent in islets infiltrated by CD45+ immune cells, suggesting a link to islet inflammation. The \u03b2-cell toxin streptozotocin (STZ) elicits DDR in islets, both in vivo and ex vivo, and causes elevation of the proinflammatory molecules IL-1\u03b2 and Cxcl10. \u03b2-Cell\u2013specific inactivation of the master DNA repair gene ataxia telangiectasia mutated (ATM) in STZ-treated mice decreases the expression of proinflammatory cytokines in islets and attenuates the development of hyperglycemia. Together, these data suggest that \u03b2-cell DDR is an early event in T1D, possibly contributing to autoimmunity.<\/jats:p>","DOI":"10.2337\/db17-1006","type":"journal-article","created":{"date-parts":[[2018,8,27]],"date-time":"2018-08-27T11:56:08Z","timestamp":1535370968000},"page":"2305-2318","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":62,"title":["\u03b2-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes"],"prefix":"10.2337","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0361-3374","authenticated-orcid":false,"given":"Elad","family":"Horwitz","sequence":"first","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, The Hebrew University, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Krogvold","sequence":"additional","affiliation":[{"name":"Paediatric Department, Oslo University Hospital HF, Faculty 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