{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:41:19Z","timestamp":1780058479275,"version":"3.54.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007247","name":"Svenska Kulturfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Diabetes is a result of an interplay between genetic, environmental and lifestyle factors. Keratin intermediate filaments are stress proteins in epithelial cells, and keratin mutations predispose to several human diseases. However, the involvement of keratins in diabetes is not well known. K8 and its partner K18 are the main \u03b2\u2010cell keratins, and knockout of K8 (K8<jats:sup>\u2212\/\u2212<\/jats:sup>) in mice causes mislocalization of glucose transporter 2, mitochondrial defects, reduced insulin content and altered systemic glucose\/insulin control. We hypothesize that K8\/K18 offer protection during \u03b2\u2010cell stress and that decreased K8 levels contribute to diabetes susceptibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>K8\u2010heterozygous knockout (K8<jats:sup>+\/\u2212<\/jats:sup>) and wild\u2010type (K8<jats:sup>+\/+<\/jats:sup>) mice were used to evaluate the influence of keratin levels on endocrine pancreatic function and diabetes development under basal conditions and after T1D streptozotocin (<jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>)\u2010induced \u03b2\u2010cell stress and T2D high\u2010fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Murine K8<jats:sup>+\/\u2212<\/jats:sup> endocrine islets express ~50% less K8\/K18 compared with K8<jats:sup>+\/+<\/jats:sup>. The decreased keratin levels have little impact on basal systemic glucose\/insulin regulation, \u03b2\u2010cell health or insulin levels. Diabetes incidence and blood glucose levels are significantly higher in K8<jats:sup>+\/\u2212<\/jats:sup> mice after low\u2010dose\/chronic <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content> treatment, and <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content> causes more \u03b2\u2010cell damage and polyuria in K8<jats:sup>+\/\u2212<\/jats:sup> compared with K8<jats:sup>+\/+<\/jats:sup>. K8 appears upregulated 5 weeks after <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content> treatment in K8<jats:sup>+\/+<\/jats:sup> islets but not in K8<jats:sup>+\/\u2212<\/jats:sup>. K8<jats:sup>+\/\u2212<\/jats:sup> mice showed no major susceptibility risk to <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content> compared to K8<jats:sup>+\/+<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Partial K8 deficiency reduces \u03b2\u2010cell stress tolerance and aggravates diabetes development in response to <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content>, while there is no major susceptibility to <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13085","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T18:19:04Z","timestamp":1525285144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Decreased levels of keratin 8 sensitize mice to streptozotocin\u2010induced diabetes"],"prefix":"10.1111","volume":"224","author":[{"given":"C. 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M.","family":"Toivola","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Cell Biology Faculty of Science and Engineering \u00c5bo Akademi University Turku Finland"},{"name":"Turku Center for Disease Modeling University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2012.9.6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0331"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60591-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes6010087"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000540"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2156-5-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37762"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00455.2016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2009.11.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.12.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0435-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2010.12.019"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20652"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e3283525cb8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075101"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39894"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.24.2964"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7a.1191"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00782"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.132795"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.11.011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700095R"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1661-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.120.3.743"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.16"},{"key":"e_1_2_8_27_1","first-page":"356","article-title":"The streptozotocin\u2010induced diabetic nude mouse model: differences between animals from different sources","volume":"61","author":"Graham ML","year":"2011","journal-title":"Comp Med"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127436"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200602146"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0431-x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27068"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep32710"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2091"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000180300004"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201008095"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.12.005"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3531"},{"key":"e_1_2_8_38_1","first-page":"e2096","article-title":"A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation","volume":"50","author":"Zmuda EJ","year":"2011","journal-title":"J. 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