{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:56:21Z","timestamp":1791410181820,"version":"4.3.3"},"reference-count":93,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["2019\u20100057194"],"award-info":[{"award-number":["2019\u20100057194"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["2020\u20100063502"],"award-info":[{"award-number":["2020\u20100063502"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Type 1 diabetes (T1D) is characterized by immune cell infiltration in the islets of Langerhans, leading to the destruction of insulin\u2010producing beta cells. This destruction is driven by secreted cytokines and cytotoxic T\u00a0cells inducing apoptosis in beta cells. Butyrate, a metabolite produced by the gut microbiota, has been shown to have various health benefits, including anti\u2010inflammatory and anti\u2010diabetic effects. In this study, we investigated the potential protective effects of butyrate on cytokine\u2010induced apoptosis in beta cells and explored the underlying mechanisms. Insulin\u2010secreting INS\u20101E cells and isolated mouse islets were treated with interleukin\u20101beta (IL\u20101\u03b2) or a combination of IL\u20101\u03b2 and interferon\u2010gamma (IFN\u2010\u03b3) in the presence or absence of butyrate. We analyzed apoptosis, nitric oxide (NO) levels, expression of stress\u2010related genes, and immune cell migration. Our results demonstrated that butyrate significantly attenuated cytokine\u2010induced apoptosis in both INS\u20101E cells and mouse islets, accompanied by a reduction in NO levels. Butyrate also decreased the expression of endoplasmic reticulum (ER) stress markers such as\n                    <jats:italic>Chop<\/jats:italic>\n                    , phosphorylated eIF2\u03b1 and\n                    <jats:italic>Atf4<\/jats:italic>\n                    , as well as some pro\u2010apoptotic genes including\n                    <jats:italic>Dp5<\/jats:italic>\n                    and\n                    <jats:italic>Puma<\/jats:italic>\n                    . Butyrate reduced the cytokine\u2010induced expression of the chemokine genes\n                    <jats:italic>Cxcl1<\/jats:italic>\n                    and\n                    <jats:italic>Cxcl10<\/jats:italic>\n                    in mouse islets, as well as the chemotactic activity of THP\u20101 monocytes toward conditioned media from IL\u20101\u03b2\u2010exposed islets. In conclusion, these findings indicate that butyrate protects beta cells from cytokine\u2010induced apoptosis and ER stress, suggesting its potential as a therapeutic agent to prevent beta cell destruction in T1D.\n                  <\/jats:p>","DOI":"10.1111\/febs.17334","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:43:47Z","timestamp":1732164227000},"page":"226-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protection of beta cells against cytokine\u2010induced apoptosis by the gut microbial metabolite butyrate"],"prefix":"10.1111","volume":"292","author":[{"given":"Kasper Suhr","family":"J\u00f8rgensen","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe Schultz","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siv Annegrethe","family":"Hjorth","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-8067","authenticated-orcid":false,"given":"Nils","family":"Billestrup","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michala","family":"Prause","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0254-y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202203150"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03860.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01291-X"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.6.5204"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00404328"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/niox.1998.0203"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.6.7523"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230701320337"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-009-0339-5"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.186"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.03.115"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.7.1116"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3669-6"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191207498"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0015"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.1.77"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0704-2"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00605-0"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910427"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102312"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2014.01.002"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr807"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10102001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03369-z"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03814"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-46"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0526"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3274-0"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2762-3"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2604-3"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01570-w"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.21"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.S97"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-020-00502-7"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2014.02.001"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041542"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17005"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1949-2"},{"key":"e_1_2_10_41_1","first-page":"210","article-title":"Suppression of HDAC2 by sodium butyrate alleviates apoptosis of kidney cells in db\/db mice and HG\u2010induced NRK\u201052E cells","volume":"45","author":"Du Y","year":"2020","journal-title":"Int J Mol Med"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2022.05.121"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2016.35"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16040529"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031572"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2020.12.003"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0562-3"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.05.010"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2615-0"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.2.452"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp700145f"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/10611860701349695"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00153.2015"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2013-1159"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinsp.2023.100303"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02838"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105170200"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.3.397"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2019.19.e9"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010699418024"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705682"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00543.2011"},{"key":"e_1_2_10_63_1","first-page":"855","article-title":"Inhibition of interferon \u03b3 signaling by the short chain fatty acid butyrate","volume":"1","author":"Klampfer L","year":"2003","journal-title":"Mol Cancer Res"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104649"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1253"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.67"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.087486"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(95)02459-X"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00265-9"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2139-z"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13598"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.4.1249-1259.2001"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03083"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.99"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.122374"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.162131"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02299.x"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-024-01273-x"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-17-0042"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2008.02577.x"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.690082"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.04087.x"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00630"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404144"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108694"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3713"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76109-y"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.9b07701"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01193-9"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11133573"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-05073-8"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.11.021"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2cs15271a"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/s30800276"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.17334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:21:32Z","timestamp":1736227292000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.17334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":93,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/febs.17334"],"URL":"https:\/\/doi.org\/10.1111\/febs.17334","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/FEBS.17334\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.17334\/v1\/review2","asserted-by":"object"}]},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]},"assertion":[{"value":"2024-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}