{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:15:37Z","timestamp":1758708937264,"version":"3.37.3"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T00:00:00Z","timestamp":1428537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81172862","81371831"],"award-info":[{"award-number":["81172862","81371831"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013286","name":"Research Fund for the Doctoral Program of Higher Education of China","doi-asserted-by":"crossref","award":["20110131110034"],"award-info":[{"award-number":["20110131110034"]}],"id":[{"id":"10.13039\/501100013286","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2010HM025"],"award-info":[{"award-number":["ZR2010HM025"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>T<\/jats:styled-content> cell immunoglobulin and mucin domain containing 4 (TIM<\/jats:styled-content>\u20104), a novel immune regulator, is selectively expressed on antigen\u2010presenting cells, especially macrophages and mature dendritic cells. Although TIM<\/jats:styled-content>\u20104 plays key roles in mutiple immune diseases, whether it is involved in type 2 diabetes mellitus (T2D<\/jats:styled-content>) remains unknown. The aim of the present study was to investigate the expression of TIM<\/jats:styled-content>\u20104 in T2D<\/jats:styled-content> and determine its significance in disease progression.<\/jats:p><\/jats:sec>Methods<\/jats:title>Peripheral blood mononuclear cells (PBMC<\/jats:styled-content>) were isolated from T2D<\/jats:styled-content> patients and healthy controls to measure TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> expression by real\u2010time polymerase chain reaction (PCR<\/jats:styled-content>), and sera were collected to determine interleukin (IL<\/jats:styled-content>)\u20101\u03b2<\/jats:italic> concentrations and other clinical indicators (high\u2010sensitivity C<\/jats:styled-content>\u2010reactive protein [hsCRP<\/jats:styled-content>], total cholesterol, low\u2010density lipoprotein cholesterol [LDL<\/jats:styled-content>\u2010C<\/jats:styled-content>], high\u2010density lipoprotein cholesterol, triglyceride, fasting glucose, HbA1c<\/jats:styled-content>, aspartate aminotransferase, and alanine aminotransferase).<\/jats:p><\/jats:sec>Results<\/jats:title>Expression of TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> was increased significantly in PBMCs<\/jats:styled-content> from T2D<\/jats:styled-content> patients compared with healthy controls. There was a positive correlation between TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> expression and serum concentrations of hsCRP<\/jats:styled-content>. However, there was a negative correlation between TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> expression and IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic> concentrations, indicating the potential role for TIM<\/jats:styled-content>\u20104 to negatively regulate IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic> production. In addition, TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> expression was negatively correlated with lowLDL<\/jats:styled-content>\u2010C<\/jats:styled-content>, and there was a tendency for a negative relationship between TIM<\/jats:styled-content>\u20104<\/jats:italic>\u2005mRNA<\/jats:styled-content> expression and HbA1c<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The results of the present study indicate that TIM<\/jats:styled-content>\u20104 contributes, at least in part, to the pathogenesis of T2D<\/jats:styled-content>, possibly by regulating IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12276","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T06:30:50Z","timestamp":1423809050000},"page":"199-205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Increased T<\/scp> cell immunoglobulin and mucin domain containing 4 (TIM<\/scp>\u20104) is negatively correlated with serum concentrations of interleukin\u20101\u03b2<\/i> in type 2 diabetes"],"prefix":"10.1111","volume":"8","author":[{"given":"Peiqing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"},{"name":"Department of Central Laboratory Zibo Central Hospital Zibo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Zibo Central Hospital Zibo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbin","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Central Laboratory Zibo Central Hospital Zibo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Immunology Key Laboratory for Experimental Teratology of Ministry of Education Shandong Provincial Key Laboratory of Infection & Immunology Shandong University School of Medicine Jinan 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