{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:01:04Z","timestamp":1793361664118,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,3,28]]},"abstract":"<jats:p>\n                    Type 1 diabetes is characterized by the infiltration of inflammatory cells into pancreatic islets of Langerhans, followed by the selective and progressive destruction of insulin-secreting beta cells. Islet-infiltrating leukocytes secrete cytokines such as IL-1\u03b2 and IFN-\u03b3, which contribute to beta cell death.\n                    <jats:italic>In vitro<\/jats:italic>\n                    evidence suggests that cytokine-induced activation of the transcription factor NF-\u03baB is an important component of the signal triggering beta cell apoptosis. To study the\n                    <jats:italic>in vivo<\/jats:italic>\n                    role of NF-\u03baB in beta cell death, we generated a transgenic mouse line expressing a degradation-resistant NF-\u03baB protein inhibitor (\u0394NI\u03baB\u03b1), acting specifically in beta cells, in an inducible and reversible manner, by using the tet-on regulation system.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , islets expressing the \u0394NI\u03baB\u03b1 protein were resistant to the deleterious effects of IL-1\u03b2 and IFN-\u03b3, as assessed by reduced NO production and beta-cell apoptosis. This effect was even more striking\n                    <jats:italic>in vivo<\/jats:italic>\n                    , where nearly complete protection against multiple low-dose streptozocin-induced diabetes was observed, with reduced intraislet lymphocytic infiltration. Our results show\n                    <jats:italic>in vivo<\/jats:italic>\n                    that beta cell-specific activation of NF-\u03baB is a key event in the progressive loss of beta cells in diabetes. Inhibition of this process could be a potential effective strategy for beta-cell protection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0508166103","type":"journal-article","created":{"date-parts":[[2006,3,21]],"date-time":"2006-03-21T21:43:45Z","timestamp":1142977425000},"page":"5072-5077","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":229,"title":["Conditional and specific NF-\u03baB blockade protects pancreatic beta cells from diabetogenic agents"],"prefix":"10.1073","volume":"103","author":[{"given":"R.","family":"Eldor","sequence":"first","affiliation":[{"name":"Departments of *Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Yeffet","sequence":"additional","affiliation":[{"name":"Departments of *Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Baum","sequence":"additional","affiliation":[{"name":"Departments of *Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Doviner","sequence":"additional","affiliation":[{"name":"Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Amar","sequence":"additional","affiliation":[{"name":"Departments of *Endocrinology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Ben-Neriah","sequence":"additional","affiliation":[{"name":"The Lautenberg Center for Immunology, Hebrew University\u2013Hadassah Medical School, Jerusalem 91120, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Christofori","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, University of Basel, 4058 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Peled","sequence":"additional","affiliation":[{"name":"The Institute of Gene Therapy, Hadassah University Hospital, Jerusalem 91120, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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