%0 Case Reports
%T Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report.
%A Zhang J
%A Juhl CR
%A Hylten-Cavallius L
%A Salling-Olsen M
%A Linneberg A
%A Holst JJ
%A Hansen T
%A Kanters JK
%A Torekov SS
%J BMC Endocr Disord
%V 20
%N 1
%D Mar 2020 13
%M 32164657
%F 3.263
%R 10.1186/s12902-020-0513-x
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>CONCLUSIONS: </B>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.