Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Long-term Consequences of Undiagnosed Celiac Seropositivity

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The Polygenic and Monogenic Basis of Blood Traits and Diseases

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: 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.

CASE PRESENTATION: 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.

CONCLUSIONS: 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.

Original languageEnglish
JournalBMC Endocrine Disorders
Volume20
Issue number1
Pages (from-to)38
ISSN1472-6823
DOIs
Publication statusPublished - 13 Mar 2020

ID: 59544466