{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T03:50:27Z","timestamp":1787629827036,"version":"build-2736575974"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UAB","award":["Dept of CDIB"],"award-info":[{"award-number":["Dept of CDIB"]}]},{"DOI":"10.13039\/501100004343","name":"Stavros Niarchos Foundation","doi-asserted-by":"crossref","award":["Stavros Niarchos Foundation"],"award-info":[{"award-number":["Stavros Niarchos Foundation"]}],"id":[{"id":"10.13039\/501100004343","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JDRF","award":["3-PDF-2017-385-A-N"],"award-info":[{"award-number":["3-PDF-2017-385-A-N"]}]},{"name":"Veteran\u2019s Administration","award":["BX001792,13F-RCS-002"],"award-info":[{"award-number":["BX001792,13F-RCS-002"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK-69455,R01 DK110292,R01 HL125353,U01 HD087198,RR031535,R01 AI139072,R01 DK074656"],"award-info":[{"award-number":["R01DK-69455,R01 DK110292,R01 HL125353,U01 HD087198,RR031535,R01 AI139072,R01 DK074656"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"USF funds: initiative","award":["0131845"],"award-info":[{"award-number":["0131845"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,20]]},"abstract":"<jats:p>\n                    Type 1 diabetes (T1D) is a consequence of autoimmune \u03b2 cell destruction, but the role of lipids in this process is unknown. We previously reported that activation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -independent phospholipase A\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2 (iPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2) modulates polarization of macrophages (M\u03a6). Hydrolysis of the\n                    <jats:italic>sn<\/jats:italic>\n                    -2 substituent of glycerophospholipids by iPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2 can lead to the generation of oxidized lipids (eicosanoids), pro- and antiinflammatory, which can initiate and amplify immune responses triggering \u03b2 cell death. As M\u03a6 are early triggers of immune responses in islets, we examined the impact of iPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2-derived lipids (iDLs) in spontaneous-T1D prone nonobese diabetic mice (NOD), in the context of M\u03a6 production and plasma abundances of eicosanoids and sphingolipids. We find that (a) M\u03a6\n                    <jats:sub>NOD<\/jats:sub>\n                    exhibit a proinflammatory lipid landscape during the prediabetic phase; (b) early inhibition or genetic reduction of iPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u03b2 reduces production of select proinflammatory lipids, promotes antiinflammatory M\u03a6 phenotype, and reduces T1D incidence; (c) such lipid changes are reflected in NOD plasma during the prediabetic phase and at T1D onset; and (d) importantly, similar lipid signatures are evidenced in plasma of human subjects at high risk for developing T1D. These findings suggest that iDLs contribute to T1D onset and identify select lipids that could be targeted for therapeutics and, in conjunction with autoantibodies, serve as early biomarkers of pre-T1D.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.138034","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T11:01:22Z","timestamp":1597834882000},"source":"Crossref","is-referenced-by-count":27,"title":["Lipid mediators and biomarkers associated with type 1 diabetes development"],"prefix":"10.1172","volume":"5","author":[{"given":"Alexander J.","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental, and Integrative Biology, and"},{"name":"Comprehensive Diabetes Center, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology (CMMB), University of South Florida, Tampa, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3222-8918","authenticated-orcid":true,"given":"Robert N.","family":"Bone","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Cardona","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology (CMMB), University of South Florida, Tampa, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology (CMMB), University of South Florida, Tampa, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying G.","family":"Tusing","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Integrative Biology, and"},{"name":"Comprehensive Diabetes Center, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Integrative Biology, and"},{"name":"Comprehensive Diabetes Center, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kokotos","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7387-2462","authenticated-orcid":true,"given":"Christina L.","family":"Graves","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-6355","authenticated-orcid":true,"given":"Clayton E.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida Health Science Center, Gainesville, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kramer","sequence":"additional","affiliation":[{"name":"Max McGee Research Center for Juvenile Diabetes, Department of Pediatrics at Medical College of Wisconsin and Children\u2019s Research Institute of Children\u2019s Hospital of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hessner","sequence":"additional","affiliation":[{"name":"Max McGee Research Center for Juvenile Diabetes, Department of Pediatrics at Medical College of Wisconsin and Children\u2019s Research Institute of Children\u2019s Hospital of Wisconsin, Milwaukee, Wisconsin, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Chalfant","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Microbiology and Molecular Biology (CMMB), University of South Florida, Tampa, Florida, USA."},{"name":"Research Service, James A. 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