{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:34:00Z","timestamp":1740126840012,"version":"3.37.3"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81500655"],"award-info":[{"award-number":["81500655"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Postdoctoral Cultivation Fund of Shanghai Pudong New Area Gongli Hospital","award":["GLBH 2017005"],"award-info":[{"award-number":["GLBH 2017005"]}]},{"name":"Talent Project of Shanghai Pudong New Area Gongli Hospital","award":["GLRb2017-01"],"award-info":[{"award-number":["GLRb2017-01"]}]},{"name":"Discipline Program of Pudong New Area Health System of Shanghai","award":["PWZxk2017-07"],"award-info":[{"award-number":["PWZxk2017-07"]}]},{"name":"Special Disease Program of Pudong New Area Health System of Shanghai","award":["PWZzb2017-22"],"award-info":[{"award-number":["PWZzb2017-22"]}]},{"name":"Scientific Research Project of Shanghai Pudong New Area Gongli Hospital","award":["2013GLQN16"],"award-info":[{"award-number":["2013GLQN16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nBackground Neonatal diabetes mellitus is likely caused by monogenic\n  mutations, several of which have been identified. INS mutations have a broad\nspectrum of clinical presentations, ranging from severe neonatal onset to\nmild adult onset, which suggests that the products of different mutant INS\nalleles behave differently and utilize distinct mechanisms to induce\ndiabetes. In this study, a neonatal diabetes mellitus patient\u2019s INS\ngene was sequenced, and functional experiments were conducted.<\/jats:p><jats:p>\nMethods The neonatal diabetes mellitus patient\u2019s genomic DNA\n  was extracted, and the patient\u2019s KCNJ11, ABCC8, and INS genes were\nsequenced. A novel mutation was identified in INS, and the open reading\nframe of this human mutant INS gene was inserted into the pMSCV-PIG plasmid.\nThe constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and\ntransfected into 293T cells to package the lentivirus. To stably overexpress\nthe mutant gene, INS-1 cells were infected with the virus. The levels of\ninsulin in the cell culture medium and cytoplasm were determined by ELISA\nand immunocytochemistry, respectively.<\/jats:p><jats:p>\nResults A heterozygous mutation, c.125T&gt;G (p. Val42Gly), was\n  identified in a neonatal diabetes mellitus patient\u2019s INS gene. The\nhuman mutant INS open reading frame was overexpressed in INS-1 cells, and\nthe mutant insulin was undetectable in the cell culture medium and\ncytoplasm.<\/jats:p><jats:p>\nConclusions The novel heterozygous activating mutation\nc.125\u2009T&gt;G (p.Val42Gly) impairs the synthesis of insulin by\npancreatic beta cells, resulting in diabetes.<\/jats:p>","DOI":"10.1055\/a-0603-3463","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T23:33:07Z","timestamp":1528759987000},"page":"182-189","source":"Crossref","is-referenced-by-count":3,"title":["A Novel c.125\u2009T&gt;G (p.Val42Gly) Mutation in The Human\nINS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin\nSynthesis"],"prefix":"10.1055","volume":"128","author":[{"given":"Fei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital,\nthe Second Military Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhua","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Linyi People's Hospital, Linyi,\nShandong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhua","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital,\nthe Second Military Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital,\nthe Second Military Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingnan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital,\nthe Second Military Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongling","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital,\nthe Second Military Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaidong","family":"Song","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Medicine, Department of Respiration and\nEndocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong\nUniversity School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanqi","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Linyi People's Hospital, Linyi,\nShandong Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2018,6,11]]},"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-0603-3463.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T23:50:44Z","timestamp":1583365844000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-0603-3463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,11]]},"references-count":0,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2020,3,4]]},"published-print":{"date-parts":[[2020,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-0603-3463","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"type":"print","value":"0947-7349"},{"type":"electronic","value":"1439-3646"}],"subject":[],"published":{"date-parts":[[2018,6,11]]}}}