Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report.
BMC Endocr Disord
; 20(1): 38, 2020 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-32164657
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
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Resistência à Insulina
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Miócitos Cardíacos
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Canal de Potássio KCNQ1
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Mutação com Ganho de Função
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Glucose
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Insulina
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Dinamarca