{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:44:34Z","timestamp":1791215074109,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Health, Labor and Welfare of Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>The adenosine triphosphate (<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>)\u2010sensitive potassium (<jats:styled-content style=\"fixed-case\">K<jats:sub>ATP<\/jats:sub><\/jats:styled-content>) channel is a key component of insulin secretion in pancreatic \u03b2\u2010cells. Activating mutations in <jats:italic><jats:styled-content style=\"fixed-case\">ABCC<\/jats:styled-content>8<\/jats:italic> encoding for the sulfonylurea receptor subunit of the <jats:styled-content style=\"fixed-case\">K<jats:sub>ATP<\/jats:sub><\/jats:styled-content> channel have been associated with the development of neonatal diabetes mellitus (<jats:styled-content style=\"fixed-case\">NDM<\/jats:styled-content>). The aim was to investigate clinical and functional characterization of the Pro1198Leu <jats:italic><jats:styled-content style=\"fixed-case\">ABCC<\/jats:styled-content>8<\/jats:italic> gene mutation associated with permanent <jats:styled-content style=\"fixed-case\">NDM<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">PNDM<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The coding regions and conserved splice sites of <jats:italic><jats:styled-content style=\"fixed-case\">KCNJ<\/jats:styled-content>11<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">ABCC<\/jats:styled-content>8<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">INS<\/jats:styled-content><\/jats:italic> were screened for mutations in a 12\u2010year\u2010old girl diagnosed with <jats:styled-content style=\"fixed-case\">PNDM<\/jats:styled-content>. The functional property of the mutant channel identified was examined with patch\u2010clamp experiments in <jats:styled-content style=\"fixed-case\">COS<\/jats:styled-content>\u20101 cells. We also investigated the difference of effectiveness between two groups of oral sulfonylureas <jats:italic>in\u00a0vitro<\/jats:italic> and in the patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a heterozygous missense mutation (c.3593 C&gt;T, Pro1198Leu) in <jats:italic><jats:styled-content style=\"fixed-case\">ABCC<\/jats:styled-content>8<\/jats:italic>. The mutated residue (P1198) is located within a putative binding site of sulfonylureas, such as tolbutamide or gliclazide. In patch\u2010clamp experiments, the mutant channel was less <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> sensitive than the wild type. Furthermore, the sensitivity to tolbutamide was also reduced in the mutant channel. In addition to the tolbutamide\/gliclazide binding site, glibenclamide is thought to also bind to another site. Glibenclamide was more effective than other sulfonylureas <jats:italic>in\u00a0vitro<\/jats:italic> and in the patient. The treatment of the patient was finally able to be switched from insulin injection to oral glibenclamide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified the Pro1198Leu <jats:italic><jats:styled-content style=\"fixed-case\">ABCC<\/jats:styled-content>8<\/jats:italic> mutation in a <jats:styled-content style=\"fixed-case\">PNDM<\/jats:styled-content> patient, and clarified the functional and clinical characterization. The present findings provide new information for understanding <jats:styled-content style=\"fixed-case\">PNDM<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.12049","type":"journal-article","created":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T02:52:34Z","timestamp":1363143154000},"page":"269-273","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and functional characterization of the <scp>P<\/scp>ro1198<scp>L<\/scp>eu <i><scp>ABCC<\/scp>8<\/i> gene mutation associated with permanent neonatal diabetes mellitus"],"prefix":"10.1111","volume":"4","author":[{"given":"Tomoyuki","family":"Takagi","sequence":"first","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Furuta","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Miyawaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Wakayama Rosai Hospital Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Shimada","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Doi","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Matsuno","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Wakayama Rosai Hospital Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nishi","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"First Department of Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuya","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Wakayama Rosai Hospital Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norishige","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Wakayama 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