Effects of insulin on the QT interval and induced arrhythmias of human cardiomycytes

Xuegang Xie; Feng Wei; Yushun Zhang; Xingye Wang; Jianhua Huo; Tingzhong Wang; Aiqun MA

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Effects of insulin on the QT interval and induced arrhythmias of human cardiomycytes

VernacularTitle:胰岛素对人心肌细胞QT间期及诱发心律失常的影响
Author: Xuegang XIE ¹ ; Feng WEI ^{1
,

2
,

3} ; Yushun ZHANG ¹ ; Xingye WANG ¹ ; Jianhua HUO ^{3
,

4
,

5} ; Tingzhong WANG ^{3
,

4
,

5} ; Aiqun MA ^{3
,

4
,

5}
Author Information

1. Department of Structural Heart Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061
2. Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an 710061
3. Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi’an 710061
4. Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi’an 710061
5. Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Publication Type:Journal Article
Keywords: human induced pluripotent stem cell; cardiomyocyte; QT interval; arrhythmia; insulin
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(2):196-201
CountryChina
Language:Chinese
Abstract: 【Objective】 To explore the effects of insulin on the QT interval and induced arrhythmias of cardiomyocytes derived from human induced pluripotent stem cells （hiPSC-CMs）. 【Methods】 Immunofluorescence staining and flow cytometry were used to analyze the purity of hiPSC-CMs. Microelectrode array （MEA） was utilized to detect the electrophysiological changes including heart rate （HR）， field potential duration （FPD， which is similar to QT interval in ECG）， FPDc （FPD corrected by HR）， conduction velocity （CV）， and spike amplitude before and after insulin treatment. The effects of E4031 on QT interval prolongation and induced arrhythmias of hiPSC-CMs were evaluated before and after treatment with insulin. 【Results】 hiPSC-CMs highly expressed myocardial specific marker cTnT. The purity of hiPSC-CMs was 97.1%. After 5-day insulin treatment of hiPSC-CMs， HR increased by （11.9±3.3）%， FPD shortened by （22.7±2.8）%， FPDc shortened by （15.6±1.6）%， and spike amplitude increased by （39.1±7.9）% when compared with untreated group， but CV remained unchanged. 10 nmol/L of E4031 could prolong the FPDc of hiPSC-CMs by （37.8±9.0）%， and 30 nmol/L of E4031 could induce arrhythmias. After insulin treatment， 10 nmol/L of E4031 prolonged the FPDc of hiPSC-CMs by （21.8±3.1）% （compared with the untreated group， insulin decreased FPDc prolongation by E4031， 37.8%±9.0% vs. 21.8%±3.1%， P<0.05）， while 30 nmol/L of E4031 did not induce arrhythmias. 【Conclusion】 Insulin can shorten the QT interval of hiPSC-CMs and significantly reduce the QT interval prolongation and the risk of arrhythmias induced by drugs.