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Loss-of-function mutations in <jats:italic>KCNQ1<\/jats:italic> causes long QT syndrome along with glucose-stimulated hyperinsulinemia, increased C-peptide and postprandial hypoglycemia. The <jats:italic>KCNE1<\/jats:italic> protein modulates Kv7.1 in cardiac myocytes, but is not expressed in beta cells. Gain-of-function mutations in <jats:italic>KCNQ1<\/jats:italic> and <jats:italic>KCNE1<\/jats:italic> shorten the action potential duration in cardiac myocytes, but their effect on beta cells and insulin secretion is unknown.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>Two patients with atrial fibrillation due to gain-of-function mutations in <jats:italic>KCNQ1<\/jats:italic> (R670K) and <jats:italic>KCNE1<\/jats:italic> (G60D) were BMI-, age-, and sex-matched to six control participants and underwent a 6-h oral glucose tolerance test (OGTT). During the OGTT, the <jats:italic>KCNQ1<\/jats:italic> gain-of-function mutation carrier had 86% lower C-peptide response after glucose stimulation compared with matched control participants (iAUC<jats:sub>360min<\/jats:sub>\u2009=\u200934\u2009pmol\/l*min VS iAUC<jats:sub>360min<\/jats:sub>\u2009=\u2009246\u2009\u00b1\u200971\u2009pmol\/l*min). The <jats:italic>KCNE1<\/jats:italic> gain-of-function mutation carrier had normal C-peptide levels.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This case story presents a patient with a gain-of-function mutation <jats:italic>KCNQ1<\/jats:italic> R670K with low glucose-stimulated C-peptide secretion, additionally suggesting involvement of the voltage-gated potassium channel <jats:italic>KCNQ1<\/jats:italic> in glucose-stimulated insulin regulation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12902-020-0513-x","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T03:02:47Z","timestamp":1584068567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report"],"prefix":"10.1186","volume":"20","author":[{"given":"Jinyi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian R.","family":"Juhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Hylten-Cavallius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Salling-Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Linneberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Juul","family":"Holst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torben","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen K.","family":"Kanters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6779-0252","authenticated-orcid":false,"given":"Signe S.","family":"Torekov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"issue":"6604","key":"513_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/384024a0","volume":"384","author":"B Attali","year":"1996","unstructured":"Attali B. 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The project was approved by The Committees on Health Research Ethics in the Capital Region of Denmark (reference number: H-4-2010-036) and was performed in accordance to the Helsinki Declaration II. Participation in the investigation was voluntary and the individuals could retract their consent to participate at any time.Clinical Trial Registration number: NCT02775513. The manuscript adheres to the CARE guidelines.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Before participation, informed written consent was obtained from all participants, which include consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38"}}