{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T10:04:41Z","timestamp":1758189881094,"version":"3.44.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta\u2010cell receptors for GLP\u20101, both of which are related to the insulin production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non\u2010diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP\u20101 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both <jats:italic>CERS2<\/jats:italic> and <jats:italic>CERS6<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non\u2010diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta\u2010cell insulin resistance due to low levels of GLP\u20101 receptors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.3792","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T12:23:20Z","timestamp":1711110200000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of sphingolipid enzymes on blood glucose levels, development of diabetes, and involvement of pericytes"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-7423","authenticated-orcid":false,"given":"Karsten","family":"Buschard","sequence":"first","affiliation":[{"name":"Department of Pathology The Bartholin Institute Rigshospitalet Copenhagen Biocenter  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knud","family":"Josefsen","sequence":"additional","affiliation":[{"name":"Department of Pathology The Bartholin Institute Rigshospitalet Copenhagen Biocenter  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Krogvold","sequence":"additional","affiliation":[{"name":"Division of Paediatric and Adolescent Medicine Oslo University Hospital  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Gerling","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Tennessee  Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Knut","family":"Dahl\u2010J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Division of Paediatric and Adolescent Medicine Oslo University Hospital  Oslo Norway"},{"name":"Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flemming","family":"Pociot","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"},{"name":"Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1007\/S00125\u2010018\u20104614\u20102"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1007\/S12017\u2010010\u20108114\u2010X"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1007\/S00125\u2010005\u20101926\u20109"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1016\/j.imlet.2003.12.010"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1371\/JOURNAL.PONE.0037771"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.3389\/FGENE.2021.630109"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1016\/J.MCE.2013.04.002"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1111\/J.1464\u20105491.2005.01613.X"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.2337\/DC06\u20102389"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1016\/s0092\u20108674(00)80546\u20102"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.3389\/FENDO.2022.1032822"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1038\/S41467\u2010018\u201003953\u2010Y"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1016\/J.CELREP.2023.112913"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1007\/S00125\u2010013\u20103155\u2010Y"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1002\/DMRR.2316"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1007\/S00125\u2010016\u20104067\u20104"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1371\/JOURNAL.PONE.0046941"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1038\/NG.3245"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1038\/S41588\u2010021\u201000880\u20105"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1038\/S41588\u2010020\u201000757\u2010Z"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1038\/S41591\u2010021\u201001542\u2010Z"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1038\/S41588\u2010021\u201000852\u20109"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.1371\/JOURNAL.PMED.1002383"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.2337\/DC23\u2010ER05"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1042\/BJ2510017"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1016\/J.SCITOTENV.2022.154657"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.3109\/08916939108997149"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.1007\/BF00418537"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.3390\/JCM10204666"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1016\/S0140\u20106736(79)92753\u20103"},{"doi-asserted-by":"publisher","key":"e_1_2_10_32_1","DOI":"10.1007\/S11892\u2010016\u20100786\u20107"},{"doi-asserted-by":"publisher","key":"e_1_2_10_33_1","DOI":"10.1038\/S41467\u2010022\u201028039\u20108"},{"doi-asserted-by":"publisher","key":"e_1_2_10_34_1","DOI":"10.1007\/BF00586458"},{"doi-asserted-by":"publisher","key":"e_1_2_10_35_1","DOI":"10.2337\/DIAB.38.10.1211"},{"doi-asserted-by":"publisher","key":"e_1_2_10_36_1","DOI":"10.1038\/S41588\u2010021\u201000931\u2010X"}],"container-title":["Diabetes\/Metabolism Research and Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.3792","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T04:41:03Z","timestamp":1758084063000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dmrr.3792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/dmrr.3792"],"URL":"https:\/\/doi.org\/10.1002\/dmrr.3792","archive":["Portico"],"relation":{},"ISSN":["1520-7552","1520-7560"],"issn-type":[{"type":"print","value":"1520-7552"},{"type":"electronic","value":"1520-7560"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3792"}}