{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:59:01Z","timestamp":1788785941573,"version":"build-2803163510"},"reference-count":54,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to \u03b2-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-\u03baB signaling and has strong antiapoptotic activities in \u03b2-cells. Although the role of A20 on NF-\u03baB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the \u03b2-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in \u03b2-cells that are not restricted to inhibition of NF-\u03baB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual \u03b2-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of \u03b2-cell survival and unveil novel mechanisms by which A20 controls \u03b2-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.<\/jats:p>","DOI":"10.1210\/me.2015-1176","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T18:00:32Z","timestamp":1449770432000},"page":"48-61","source":"Crossref","is-referenced-by-count":31,"title":["A20 Inhibits \u03b2-Cell Apoptosis by Multiple Mechanisms and Predicts Residual \u03b2-Cell Function in Type 1 Diabetes"],"prefix":"10.1210","volume":"30","author":[{"given":"Makiko","family":"Fukaya","sequence":"first","affiliation":[{"name":"Universit\u00e9 Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A.","family":"Brorsson","sequence":"additional","affiliation":[{"name":"Copenhagen Diabetes Research Center (C.A.B., L.B.N., M.L.A., H.B.M., F.P., J.S.), Department of Pediatrics E, Copenhagen University Hospital Herlev, DL-2730 Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira","family":"Meyerovich","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen","family":"Catrysse","sequence":"additional","affiliation":[{"name":"Inflammation Research Center (L.C., R.B., G.v.L.), Vlaams Instituut voor Biotechnologie, 9052 Gent, Belgium"},{"name":"Department of Biomedical Molecular Biology (L.C., R.B., G.v.L.), 9052 Gent University, Gent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Delaroche","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerielle C.","family":"Vanzela","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Libre de Bruxelles Center for Diabetes Research (M.F., K.M., D.D., E.C.V., A.K.C.), Free University Brussels, 1070 Brussels, Belgium"},{"name":"Laboratory of Endocrine Pancreas and Metabolism (E.C.V.), Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, 13083-970 Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Ortis","sequence":"additional","affiliation":[{"name":"Department of Development and Cellular Biology (F.O.), Institute of Biomedical Sciences, 05508-900 S\u00e3o Paulo University, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Beyaert","sequence":"additional","affiliation":[{"name":"Inflammation Research Center (L.C., 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