Key result
KCNQ1 gain-of-function mutation linked to ~86% lower C-peptide response to glucose stimulation versus matched controls.
Why the study?
The effect of gain-of-function mutations in KCNQ1 and KCNE1 on beta cell insulin secretion and glucose-stimulated insulin regulation is unknown.
Do gain-of-function mutations in KCNQ1 and KCNE1 affect glucose-stimulated C-peptide secretion in patients with atrial fibrillation?
Case Report (n=8)
Do gain-of-function mutations in KCNQ1 and KCNE1 affect glucose-stimulated C-peptide secretion in patients with atrial fibrillation?
Effect estimate: 86% lower
Absolute Event Rate: 34% vs 246%
A gain-of-function mutation in KCNQ1 (R670K) is associated with low glucose-stimulated C-peptide secretion, suggesting its involvement in insulin regulation.
Supports KCNQ1 investigation in insulin secretion; hypothesis-generating only and should not change AF practice.
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.
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Zhang et al. (2020) conducted a case report in Atrial fibrillation with gain-of-function mutations in KCNQ1 or KCNE1 (n=8). Gain-of-function mutation in KCNQ1 (R670K) vs. Matched control participants was evaluated on C-peptide response after glucose stimulation (iAUC360min) (86% lower). The KCNQ1 gain-of-function mutation carrier had an 86% lower C-peptide response after glucose stimulation compared with matched control participants.
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