{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:47:18Z","timestamp":1783529238663,"version":"3.55.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R002517\/1"],"award-info":[{"award-number":["BB\/R002517\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R017220\/1"],"award-info":[{"award-number":["BB\/R017220\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T002107\/1"],"award-info":[{"award-number":["MR\/T002107\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["CTSA UL1 TR000430"],"award-info":[{"award-number":["CTSA UL1 TR000430"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["DRTC P30DK020595"],"award-info":[{"award-number":["DRTC P30DK020595"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["K23DK094866"],"award-info":[{"award-number":["K23DK094866"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK104942"],"award-info":[{"award-number":["R01DK104942"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinical Therapeutics Training Grant","award":["T32GM00719"],"award-info":[{"award-number":["T32GM00719"]}]},{"DOI":"10.13039\/100015602","name":"Kovler Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>The ATP-sensitive potassium (K<jats:sub>ATP<\/jats:sub>) channel couples beta cell electrical activity to glucose-stimulated insulin secretion. Loss-of-function mutations in either the pore-forming (inwardly rectifying potassium channel 6.2 [Kir6.2], encoded by <jats:italic>KCNJ11<\/jats:italic>) or regulatory (sulfonylurea receptor 1, encoded by <jats:italic>ABCC8<\/jats:italic>) subunits result in congenital hyperinsulinism, whereas gain-of-function mutations cause neonatal diabetes. Here, we report a novel loss-of-function mutation (Ser118Leu) in the pore helix of Kir6.2 paradoxically associated with sulfonylurea-sensitive diabetes that presents in early adult life.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A 31-year-old woman was diagnosed with mild hyperglycaemia during an employee screen. After three pregnancies, during which she was diagnosed with gestational diabetes, the patient continued to show elevated blood glucose and was treated with glibenclamide (known as glyburide in the USA and Canada) and metformin. Genetic testing identified a heterozygous mutation (S118L) in the <jats:italic>KCNJ11<\/jats:italic> gene. Neither parent was known to have diabetes. We investigated the functional properties and membrane trafficking of mutant and wild-type K<jats:sub>ATP<\/jats:sub> channels in <jats:italic>Xenopus<\/jats:italic> oocytes and in HEK-293T cells, using patch-clamp, two-electrode voltage-clamp and surface expression assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Functional analysis showed no changes in the ATP sensitivity or metabolic regulation of the mutant channel. However, the Kir6.2-S118L mutation impaired surface expression of the K<jats:sub>ATP<\/jats:sub> channel by 40%, categorising this as a loss-of-function mutation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>Our data support the increasing evidence that individuals with mild loss-of-function K<jats:sub>ATP<\/jats:sub> channel mutations may develop insulin deficiency in early adulthood and even frank diabetes in middle age. In this case, the patient may have had hyperinsulinism that escaped detection in early life. Our results support the importance of functional analysis of K<jats:sub>ATP<\/jats:sub> channel mutations in cases of atypical diabetes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-024-06103-w","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T01:02:05Z","timestamp":1708131725000},"page":"940-951","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A loss-of-function mutation in KCNJ11 causing sulfonylurea-sensitive diabetes in early adult life"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4462-5865","authenticated-orcid":false,"given":"Natascia","family":"Vedovato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-6603","authenticated-orcid":false,"given":"Maria V.","family":"Salguero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-3567","authenticated-orcid":false,"given":"Siri Atma W.","family":"Greeley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1317-5825","authenticated-orcid":false,"given":"Christine H.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-3607","authenticated-orcid":false,"given":"Louis H.","family":"Philipson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6970-1767","authenticated-orcid":false,"given":"Frances M.","family":"Ashcroft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"issue":"1","key":"6103_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physrev.00008.2017","volume":"98","author":"P Rorsman","year":"2018","unstructured":"Rorsman P, Ashcroft FM (2018) Pancreatic \u03b2-cell electrical activity and insulin secretion: of mice and men. Physiol Rev 98(1):117\u2013214. https:\/\/doi.org\/10.1152\/physrev.00008.2017","journal-title":"Physiol Rev"},{"issue":"1","key":"6103_CR2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1152\/physrev.00022.2003","volume":"84","author":"MJ Dunne","year":"2004","unstructured":"Dunne MJ, Cosgrove KE, Shepherd RM, Aynsley-Green A, Lindley KJ (2004) Hyperinsulinism in infancy: from basic science to clinical disease. Physiol Rev 84(1):239\u2013275. https:\/\/doi.org\/10.1152\/physrev.00022.2003","journal-title":"Physiol Rev"},{"key":"6103_CR3","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1159\/000076933","volume":"61","author":"KE Cosgrove","year":"2004","unstructured":"Cosgrove KE, Shepherd RM, Fernandez EM et al (2004) Genetics and pathophysiology of hyperinsulinism in infancy. Horm Res 61:270\u2013288. https:\/\/doi.org\/10.1159\/000076933","journal-title":"Horm Res"},{"issue":"5","key":"6103_CR4","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1002\/humu.23995","volume":"41","author":"E De Franco","year":"2020","unstructured":"De Franco E, Saint-Martin C, Brusgaard K et al (2020) Update of variants identified in the pancreatic \u03b2-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. Hum Mutat 41(5):884\u2013905. https:\/\/doi.org\/10.1002\/humu.23995","journal-title":"Hum Mutat"},{"key":"6103_CR5","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/s41574-020-0351-y","volume":"16","author":"T Pipatpolkai","year":"2020","unstructured":"Pipatpolkai T, Usher S, Stansfeld PJ, Ashcroft FM (2020) New insights into KATP channel gene mutations and neonatal diabetes. Nat Rev Endocrinol 16:378\u2013393. https:\/\/doi.org\/10.1038\/s41574-020-0351-y","journal-title":"Nat Rev Endocrinol"},{"issue":"9","key":"6103_CR6","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.2337\/diabetes.54.9.2503","volume":"54","author":"AT Hattersley","year":"2005","unstructured":"Hattersley AT, Ashcroft FM (2005) Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights and new therapy. Diabetes 54(9):2503\u20132513. https:\/\/doi.org\/10.2337\/diabetes.54.9.2503","journal-title":"Diabetes"},{"issue":"5","key":"6103_CR7","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1056\/NEJMoa061759","volume":"355","author":"ER Pearson","year":"2006","unstructured":"Pearson ER, Flechtner I, Nj\u00f8lst\u00e5d PR et al (2006) Neonatal Diabetes International Collaborative Group (2006) Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. New Engl J Med 355(5):467\u2013477. https:\/\/doi.org\/10.1056\/NEJMoa061759","journal-title":"New Engl J Med"},{"issue":"2","key":"6103_CR8","doi-asserted-by":"publisher","first-page":"E355","DOI":"10.1210\/jc.2012-2169","volume":"98","author":"KE Snider","year":"2013","unstructured":"Snider KE, Becker S, Boyajian L et al (2013) Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab 98(2):E355\u2013E363. https:\/\/doi.org\/10.1210\/jc.2012-2169","journal-title":"J Clin Endocrinol Metab"},{"key":"6103_CR9","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1210\/jc.2004-1604","volume":"90","author":"MJ Henwood","year":"2005","unstructured":"Henwood MJ, Kelly A, Macmullen C et al (2005) Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes. J Clin Endocrinol Metab 90:789\u2013794. https:\/\/doi.org\/10.1210\/jc.2004-1604","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"6103_CR10","doi-asserted-by":"publisher","first-page":"11096","DOI":"10.1074\/jbc.M312810200","volume":"279","author":"F Yan","year":"2004","unstructured":"Yan F, Lin CW, Weisiger E, Cartier EA, Taschenberger G, Shyng SL (2004) Sulfonylureas correct trafficking defects of ATP-sensitive potassium channels caused by mutations in the sulfonylurea receptor. J Biol Chem 279(12):11096\u201311105. https:\/\/doi.org\/10.1074\/jbc.M312810200","journal-title":"J Biol Chem"},{"issue":"9","key":"6103_CR11","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.2337\/db07-0150","volume":"56","author":"FF Yan","year":"2007","unstructured":"Yan FF, Lin YW, MacMullen C, Ganguly A, Stanley CA, Shyng SL (2007) Congenital hyperinsulinism associated ABCC8 mutations that cause defective trafficking of ATP-sensitive K+ channels: identification and rescue. Diabetes 56(9):2339\u20132348. https:\/\/doi.org\/10.2337\/db07-0150","journal-title":"Diabetes"},{"key":"6103_CR12","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3389\/fphys.2013.00386","volume":"4","author":"GM Martin","year":"2013","unstructured":"Martin GM, Chen PC, Devaraneni P, Shyng SL (2013) Pharmacological rescue of trafficking-impaired ATP-sensitive potassium channels. Front Physiol 4:386. https:\/\/doi.org\/10.3389\/fphys.2013.00386","journal-title":"Front Physiol"},{"issue":"8","key":"6103_CR13","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1172\/JCI35414","volume":"118","author":"SE Pinney","year":"2008","unstructured":"Pinney SE, MacMullen C, Becker S et al (2008) Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J Clin Invest 118(8):2877\u20132886. https:\/\/doi.org\/10.1172\/JCI35414","journal-title":"J Clin Invest"},{"issue":"10","key":"6103_CR14","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1007\/s00125-011-2207-4","volume":"54","author":"RR Kapoor","year":"2011","unstructured":"Kapoor RR, Flanagan SE, James CT et al (2011) Hyperinsulinaemic hypoglycaemia and diabetes mellitus due to dominant ABCC8\/KCNJ11 mutations. Diabetologia 54(10):2575\u20132583. https:\/\/doi.org\/10.1007\/s00125-011-2207-4","journal-title":"Diabetologia"},{"issue":"9354","key":"6103_CR15","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S0140-6736(03)12325-2","volume":"361","author":"H Huopio","year":"2003","unstructured":"Huopio H, Otonkoski T, Vauhkonen I, Reimann F, Ashcroft FM, Laakso M (2003) A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Lancet 361(9354):301\u2013307. https:\/\/doi.org\/10.1016\/S0140-6736(03)12325-2","journal-title":"Lancet"},{"issue":"7","key":"6103_CR16","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.2337\/db08-0159","volume":"57","author":"M Abdulhadi-Atwan","year":"2008","unstructured":"Abdulhadi-Atwan M, Bushman J, Tornovsky-Babaey S et al (2008) Novel de novo mutation in sulfonylurea receptor 1 presenting as hyperinsulinism in infancy followed by overt diabetes in early adolescence. Diabetes 57(7):1935\u20131940. https:\/\/doi.org\/10.2337\/db08-0159","journal-title":"Diabetes"},{"issue":"1","key":"6103_CR17","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s12020-020-02585-x","volume":"72","author":"ZD Xu","year":"2021","unstructured":"Xu ZD, Hui PP, Zhang W et al (2021) Analysis of clinical and genetic characteristics of Chinese children with congenital hyperinsulinemia that is spontaneously relieved. Endocrine 72(1):116\u2013123. https:\/\/doi.org\/10.1007\/s12020-020-02585-x","journal-title":"Endocrine"},{"issue":"4","key":"6103_CR18","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1159\/000284394","volume":"73","author":"A Kumaran","year":"2010","unstructured":"Kumaran A, Kapoor RR, Flanagan SE, Ellard S, Hussain K (2010) Congenital hyperinsulinism due to a compound heterozygous ABCC8 mutation with spontaneous resolution at eight weeks. Horm Res Paediatr 73(4):287\u2013292. https:\/\/doi.org\/10.1159\/000284394","journal-title":"Horm Res Paediatr"},{"issue":"1","key":"6103_CR19","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s13023-016-0547-3","volume":"11","author":"M Salomon-Estebanez","year":"2016","unstructured":"Salomon-Estebanez M, Flanagan SE, Ellard S et al (2016) Conservatively treated congenital hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time. Orphanet J Rare Dis 11(1):163. https:\/\/doi.org\/10.1186\/s13023-016-0547-3","journal-title":"Orphanet J Rare Dis"},{"key":"6103_CR20","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1111\/j.1399-5448.2009.00626.x","volume":"11","author":"TC Vieira","year":"2010","unstructured":"Vieira TC, Bergamin CS, Gurgel LC, Mois\u00e9s RS (2010) Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation. Pediatr Diabetes 11:505\u2013508. https:\/\/doi.org\/10.1111\/j.1399-5448.2009.00626.x","journal-title":"Pediatr Diabetes"},{"issue":"6","key":"6103_CR21","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.2337\/dc07-2059","volume":"31","author":"M Gussinyer","year":"2008","unstructured":"Gussinyer M, Clemente M, Cebri\u00e1n R, Yeste D, Albisu M, Carrascosa A (2008) Glucose intolerance and diabetes are observed in the long-term follow-up of nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene. Diabetes Care 31(6):1257\u20131259. https:\/\/doi.org\/10.2337\/dc07-2059","journal-title":"Diabetes Care"},{"key":"6103_CR22","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1210\/jcem.80.2.7852494","volume":"80","author":"G Leibowitz","year":"1995","unstructured":"Leibowitz G, Glaser B, Higazi AA, Salameh M, Cerasi E, Landau H (1995) Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up. J Clin Endocrinol Metab 80:386\u2013392. https:\/\/doi.org\/10.1210\/jcem.80.2.7852494","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"6103_CR23","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1007\/s00125-013-3031-9","volume":"56","author":"L Liu","year":"2013","unstructured":"Liu L, Nagashima K, Yasuda T et al (2013) Mutations in KCNJ11 are associated with the development of autosomal dominant, early-onset type 2 diabetes. Diabetologia 56(12):2609\u201318. https:\/\/doi.org\/10.1007\/s00125-013-3031-9","journal-title":"Diabetologia"},{"issue":"18","key":"6103_CR24","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1093\/hmg\/ddi305","volume":"14","author":"P Proks","year":"2005","unstructured":"Proks P, Girard C, Ashcroft FM (2005) Functional effects of KCNJ11 mutations causing neonatal diabetes: enhanced activation by MgATP. Hum Mol Genet 14(18):2717\u20132726. https:\/\/doi.org\/10.1093\/hmg\/ddi305","journal-title":"Hum Mol Genet"},{"issue":"1","key":"6103_CR25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1113\/jphysiol.1997.sp021843","volume":"498","author":"FM Gribble","year":"1997","unstructured":"Gribble FM, Ashfield R, \u00c4mm\u00e4l\u00e4 C, Ashcroft FM (1997) Properties of cloned ATP-sensitive K-currents expressed in Xenopus oocytes. J Physiol 498(1):87\u201398. https:\/\/doi.org\/10.1113\/jphysiol.1997.sp021843","journal-title":"J Physiol"},{"issue":"4","key":"6103_CR26","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1085\/jgp.201010475","volume":"136","author":"P Proks","year":"2010","unstructured":"Proks P, de Wet H, Ashcroft FM (2010) Activation of the KATP channel by Mg-nucleotide interaction with SUR1. J Gen Physiol 136(4):389\u2013405. https:\/\/doi.org\/10.1085\/jgp.201010475","journal-title":"J Gen Physiol"},{"issue":"3","key":"6103_CR27","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/s0896-6273(00)80708-4","volume":"22","author":"N Zerangue","year":"1999","unstructured":"Zerangue N, Schwappach B, Jan YN, Jan LY (1999) A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels. Neuron 22(3):537\u2013548. https:\/\/doi.org\/10.1016\/s0896-6273(00)80708-4","journal-title":"Neuron"},{"key":"6103_CR28","doi-asserted-by":"publisher","first-page":"bcr2013008767","DOI":"10.1136\/bcr-2013-008767","volume":"2013","author":"D Khoriati","year":"2013","unstructured":"Khoriati D, Arya VB, Flanagan SE, Ellard S, Hussain K (2013) Prematurity, macrosomia, hyperinsulinaemic hypoglycaemia and a dominant ABCC8 gene mutation. BMJ Case Rep 2013:bcr2013008767. https:\/\/doi.org\/10.1136\/bcr-2013-008767","journal-title":"BMJ Case Rep"},{"key":"6103_CR29","doi-asserted-by":"publisher","first-page":"4450","DOI":"10.1210\/jc.2004-0441","volume":"89","author":"SN Magge","year":"2004","unstructured":"Magge SN, Shyng SL, MacMullen C, Steinkrauss L, Ganguly A, Katz LE, Stanley CA (2004) Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor. J Clin Endocrinol Metab 89:4450\u20136. https:\/\/doi.org\/10.1210\/jc.2004-0441","journal-title":"J Clin Endocrinol Metab"},{"key":"6103_CR30","doi-asserted-by":"publisher","first-page":"3654618","DOI":"10.1155\/2019\/3654618","volume":"2019","author":"T Koufakis","year":"2019","unstructured":"Koufakis T et al (2019) First report of diabetes phenotype due to a loss-of-function ABCC8 mutation previously known to cause congenital hyperinsulinism. Case Rep Genet 2019:3654618. https:\/\/doi.org\/10.1155\/2019\/3654618","journal-title":"Case Rep Genet"},{"key":"6103_CR31","doi-asserted-by":"publisher","first-page":"e118","DOI":"10.1371\/journal.pmed.0040118","volume":"4","author":"ER Pearson","year":"2007","unstructured":"Pearson ER, Boj SF, Steele AM et al (2007) Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med 4:e118. https:\/\/doi.org\/10.1371\/journal.pmed.0040118","journal-title":"PLoS Med"},{"issue":"10","key":"6103_CR32","doi-asserted-by":"publisher","first-page":"E2026","DOI":"10.1210\/jc.2012-1356","volume":"97","author":"DE Stanescu","year":"2012","unstructured":"Stanescu DE, Hughes N, Kaplan B, Stanley CA, De Le\u00f3n DD (2012) Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab 97(10):E2026-30. https:\/\/doi.org\/10.1210\/jc.2012-1356","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"6103_CR33","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.stem.2022.12.001","volume":"30","author":"FM Hermann","year":"2022","unstructured":"Hermann FM, Kj\u00e6rgaard MF, Tian C et al (2022) An insulin hypersecretion phenotype precedes pancreatic b-cell failure in MODY3 patient-specific cells. Cell Stem Cell 30(1):38-51.e8. https:\/\/doi.org\/10.1016\/j.stem.2022.12.001","journal-title":"Cell Stem Cell"},{"issue":"26","key":"6103_CR34","doi-asserted-by":"publisher","first-page":"16992","DOI":"10.1073\/pnas.012479199","volume":"99","author":"JC Koster","year":"2002","unstructured":"Koster JC, Remedi MS, Flagg TP et al (2002) Hyperinsulinism induced by targeted suppression of beta cell KATP channels. Proc Natl Acad Sci 99(26):16992\u201316997. https:\/\/doi.org\/10.1073\/pnas.012479199","journal-title":"Proc Natl Acad Sci"},{"issue":"10","key":"6103_CR35","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1007\/s00125-006-0367-4","volume":"49","author":"MS Remedi","year":"2006","unstructured":"Remedi MS, Rocheleau JV, Tong A et al (2006) Hyperinsulinism in mice with heterozygous loss of K(ATP) channels. Diabetologia 49(10):2368\u20132378. https:\/\/doi.org\/10.1007\/s00125-006-0367-4","journal-title":"Diabetologia"},{"issue":"18","key":"6103_CR36","doi-asserted-by":"publisher","first-page":"10402","DOI":"10.1073\/pnas.95.18.10402","volume":"95","author":"T Miki","year":"1998","unstructured":"Miki T, Nagashima K, Tashiro F et al (1998) Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci 95(18):10402\u201310406. https:\/\/doi.org\/10.1073\/pnas.95.18.10402","journal-title":"Proc Natl Acad Sci"},{"issue":"13","key":"6103_CR37","doi-asserted-by":"publisher","first-page":"9270","DOI":"10.1074\/jbc.275.13.9270","volume":"275","author":"V Seghers","year":"2000","unstructured":"Seghers V, Nakazaki M, DeMayo F, Aguilar-Bryan L, Bryan J (2000) Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion. J Biol Chem 275(13):9270\u20139277. https:\/\/doi.org\/10.1074\/jbc.275.13.9270","journal-title":"J Biol Chem"},{"issue":"12","key":"6103_CR38","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.2337\/diabetes.53.12.3159","volume":"53","author":"MS Remedi","year":"2004","unstructured":"Remedi MS, Koster JC, Markova K et al (2004) Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K channels. Diabetes 53(12):3159\u20133167. https:\/\/doi.org\/10.2337\/diabetes.53.12.3159","journal-title":"Diabetes"},{"issue":"11","key":"6103_CR39","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.2337\/db12-1611","volume":"62","author":"K Shimomura","year":"2013","unstructured":"Shimomura K, Tusa M, Iberl M et al (2013) A mouse model of human hyperinsulinism produced by the E1506K mutation in the sulphonylurea receptor SUR1. Diabetes 62(11):3797\u20133806. https:\/\/doi.org\/10.2337\/db12-1611","journal-title":"Diabetes"},{"issue":"11","key":"6103_CR40","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1007\/s00125-010-1866-x","volume":"53","author":"A Hugill","year":"2010","unstructured":"Hugill A, Shimomura K, Ashcroft FM, Cox RD (2010) A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose-intolerant phenotype in the mouse. Diabetologia 53(11):2352\u20132356. https:\/\/doi.org\/10.1007\/s00125-010-1866-x","journal-title":"Diabetologia"},{"issue":"3","key":"6103_CR41","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2337\/db21-0755","volume":"71","author":"CG Nichols","year":"2022","unstructured":"Nichols CG, York NW, Remedi MS (2022) ATP-sensitive potassium channels in hyperinsulinism and type 2 diabetes: inconvenient paradox or new paradigm? Diabetes 71(3):367\u2013375. https:\/\/doi.org\/10.2337\/db21-0755","journal-title":"Diabetes"},{"key":"6103_CR42","doi-asserted-by":"publisher","first-page":"e32481","DOI":"10.7554\/eLife.32481","volume":"6","author":"KPK Lee","year":"2017","unstructured":"Lee KPK, Chen J, MacKinnon R (2017) Molecular structure of human KATP in complex with ATP and ADP. eLife 6:e32481. https:\/\/doi.org\/10.7554\/eLife.32481","journal-title":"eLife"},{"issue":"48","key":"6103_CR43","doi-asserted-by":"publisher","first-page":"e2112267118","DOI":"10.1073\/pnas.2112267118","volume":"118","author":"C Zhao","year":"2021","unstructured":"Zhao C, MacKinnon R (2021) Molecular structure of an open human K ATP channel. Proc Natl Acad Sci 118(48):e2112267118. https:\/\/doi.org\/10.1073\/pnas.2112267118","journal-title":"Proc Natl Acad Sci"},{"key":"6103_CR44","doi-asserted-by":"publisher","unstructured":"Driggers CM, Kuo YY, Zhu P, ElSheikh A, Shyng S-L (2023) Structure of an open KATP channel reveals tandem PIP2 binding sites mediating the Kir6.2 and SUR1 regulatory interface. bioRxiv preprint. https:\/\/doi.org\/10.1101\/2023.08.01.551546","DOI":"10.1101\/2023.08.01.551546"},{"key":"6103_CR45","doi-asserted-by":"publisher","first-page":"e31054","DOI":"10.7554\/eLife.3105410.7554\/eLife.31054","volume":"6","author":"GM Martin","year":"2017","unstructured":"Martin GM, Kandasamy B, DiMaio F, Yoshioka C, Shyng SL (2017) Anti-diabetic drug binding site in a mammalian KATP channel revealed by Cryo-EM. eLife 6:e31054. https:\/\/doi.org\/10.7554\/eLife.3105410.7554\/eLife.31054","journal-title":"eLife"},{"key":"6103_CR46","doi-asserted-by":"publisher","first-page":"4113","DOI":"10.1016\/j.febslet.2005.06.039","volume":"579","author":"K Yang","year":"2005","unstructured":"Yang K, Fang K, Fromondi L, Chan KW (2005) Low temperature completely rescues the function of two misfolded KATP channel disease-mutants. FEBS Lett 579:4113\u20134118. https:\/\/doi.org\/10.1016\/j.febslet.2005.06.039","journal-title":"FEBS Lett"},{"key":"6103_CR47","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46417","volume":"8","author":"GM Martin","year":"2019","unstructured":"Martin GM, Sung MW, Yang Z et al (2019) Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM. Elife 8:e46417. https:\/\/doi.org\/10.7554\/eLife.46417","journal-title":"Elife"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06103-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-024-06103-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06103-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T09:49:29Z","timestamp":1710928169000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-024-06103-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,17]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["6103"],"URL":"https:\/\/doi.org\/10.1007\/s00125-024-06103-w","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,17]]},"assertion":[{"value":"25 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We thank the patient for her participation.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The datasets generated during the current study are available from the corresponding author.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"NV and FMA are supported by UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) (BB\/R002517\/1 and BB\/R017220\/1). FMA is also supported by the Medical Research Council (MRC) (MR\/T002107\/1). This work was also supported by the US National Institutes of Health R01DK104942 (LHP\/SAWG), NIH DRTC P30DK020595, NIH K23DK094866 (SAWG), NIH CTSA UL1 TR000430 (REDCap support), and gifts from the Kovler Family Foundation. MVS is supported by Clinical Therapeutics Training Grant (T32GM007019).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"NV, FMA and LHP designed the study. LHP, CHY, SAWG and MVS identified the mutation and collected and analysed the genetic and clinical data. NV collected and analysed the patch-clamp, two-electrode voltage-clamp and western blot data. FMA, NV, LHP, SAWG and MVS wrote the manuscript. All authors critically revised the paper and approved the final version. FMA is the guarantor of the electrophysiological studies, and LHP is the guarantor of the genetic studies.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}