The voltage-gated potassium channel Kv7.1 encoded by KCNQ1 is located in both cardiac myocytes and insulin producing beta cells. Loss-of-function mutations in KCNQ1 causes long QT syndrome along with glucose-stimulated hyperinsulinemia, increased C-peptide and postprandial hypoglycemia. The KCNE1 protein modulates Kv7.1 in cardiac myocytes, but is not expressed in beta cells. Gain-of-function mutations in KCNQ1 and KCNE1 shorten the action potential duration in cardiac myocytes, but their effect on beta cells and insulin secretion is unknown. Two patients with atrial fibrillation due to gain-of-function mutations in KCNQ1 (R670K) and KCNE1 (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 KCNQ1 gain-of-function mutation carrier had 86% lower C-peptide response after glucose stimulation compared with matched control participants (iAUC360min = 34 pmol/l*min VS iAUC360min = 246 ± 71 pmol/l*min). The KCNE1 gain-of-function mutation carrier had normal C-peptide levels. This case story presents a patient with a gain-of-function mutation KCNQ1 R670K with low glucose-stimulated C-peptide secretion, additionally suggesting involvement of the voltage-gated potassium channel KCNQ1 in glucose-stimulated insulin regulation.

中文翻译：

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电压门控钾通道基因KCNQ1的功能获得性突变和葡萄糖刺激的低胰岛素血症-病例报告

由KCNQ1编码的电压门控钾通道Kv7.1位于心肌细胞和胰岛素产生β细胞中。KCNQ1的功能丧失突变引起长时间的QT综合征，以及葡萄糖刺激的高胰岛素血症，C肽增加和餐后低血糖。KCNE1蛋白调节心肌细胞中的Kv7.1，但在β细胞中不表达。KCNQ1和KCNE1中的功能获得性突变缩短了心肌细胞中动作电位的持续时间，但是它们对β细胞和胰岛素分泌的作用尚不清楚。两名因KCNQ1（R670K）和KCNE1（G60D）功能获得性突变而发生房颤的患者与6名对照参与者进行了BMI，年龄和性别匹配，并接受了6小时口服葡萄糖耐量测试（OGTT ）。在OGTT期间，与匹配的对照组参与者相比，葡萄糖刺激后KCNQ1功能获得性突变载体的C肽应答降低了86％（iAUC360min = 34 pmol / l * min VS iAUC360min = 246±71 pmol / l * min）。KCNE1功能获得突变载体具有正常的C肽水平。该案例介绍了一名患者，其功能获得性突变KCNQ1 R670K具有低葡萄糖刺激的C肽分泌，另外提示电压门控钾通道KCNQ1参与了葡萄糖刺激的胰岛素调节。