The role of acute hyperinsulinemia in the development of cardiac arrhythmias

Drimba, László; Döbrönte, Róbert; Hegedűs, Csaba; Sári, Réka; Yin, Dong; Nemeth, J.; Szilvássy, Zoltán; Peitl, Barna

doi:10.1007/s00210-013-0845-4

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…In particular, RIMS1 has been reported to regulate insulin secretory machinery [ 50 ]. Since insulin infusion has been shown to cause QTc prolongation in animal models [ 51 , 52 ], this gene may be more likely to play a pathogenic role in LQTS.…”

Section: Discussionmentioning

confidence: 99%

Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes

et al. 2015

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Long QT syndrome (LQTS) is an arrhythmogenic disorder that can lead to sudden death. To date, mutations in 15 LQTS-susceptibility genes have been implicated. However, the genetic cause for approximately 20% of LQTS patients remains elusive. Here, we performed whole-exome sequencing analyses on 59 LQTS and 61 unaffected individuals in 35 families and 138 unrelated LQTS cases, after genetic screening of known LQTS genes. Our systematic analysis of familial cases and subsequent verification by Sanger sequencing identified 92 candidate mutations in 88 genes for 23 of the 35 families (65.7%): these included eleven de novo, five recessive (two homozygous and three compound heterozygous) and seventy-three dominant mutations. Although no novel commonly mutated gene was identified other than known LQTS genes, protein-protein interaction (PPI) network analyses revealed ten new pathogenic candidates that directly or indirectly interact with proteins encoded by known LQTS genes. Furthermore, candidate gene based association studies using an independent set of 138 unrelated LQTS cases and 587 controls identified an additional novel candidate. Together, mutations in these new candidates and known genes explained 37.1% of the LQTS families (13 in 35). Moreover, half of the newly identified candidates directly interact with calmodulin (5 in 11; comparison with all genes; p=0.042). Subsequent variant analysis in the independent set of 138 cases identified 16 variants in the 11 genes, of which 14 were in calmodulin-interacting genes (87.5%). These results suggest an important role of calmodulin and its interacting proteins in the pathogenesis of LQTS.

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Section: Discussionmentioning

confidence: 99%

Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes

et al. 2015

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“…Review of related literature Socio-demographics are nothing more than characteristics of a population (Drimba et al, 2013). Generally, characteristics such as age, gender, ethnicity, education level, income, type of client, years of experience in utilisation healthcare service, location to health facility and health insurance status are some socio-demographics that influence health-seeking behaviour (Drimba et al, 2013;Dapaah and Nachinaab, 2019). However, how these characteristic influence patients' health-seeking behaviour in regard to the kind of health facility to access, whether private or public, has not been fully addressed in the literature.…”

Section: Theoretical Approachmentioning

confidence: 99%

“…Socio-demographics are nothing more than characteristics of a population (Drimba et al , 2013). Generally, characteristics such as age, gender, ethnicity, education level, income, type of client, years of experience in utilisation healthcare service, location to health facility and health insurance status are some socio-demographics that influence health-seeking behaviour (Drimba et al , 2013; Dapaah and Nachinaab, 2019).…”

Section: Review Of Related Literaturementioning

confidence: 99%

The influence of sociodemographic behavioural variables on health-seeking behaviour and the utilisation of public and private hospitals in Ghana

Adongo

Dapaah

Azumah

et al. 2021

IJSSP

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PurposeSeveral studies have described health-seeking behaviour within the context of various diseases, the health status and age group. However, knowledge on patient health-seeking behaviour in the use of public and private hospitals and socio-demographic characteristics in developing countries is still scarce. This paper examines the influence of socio-demographic behavioural variables on health-seeking behaviour and the use of public and private health facilities in Ghana.Design/methodology/approachQuantitative research approach uses the modified SERVQUAL dimension as a data collection tool. Descriptive statistics with Pearson's chi-square test were conducted to determine the relationship between socio-demographic behavioural variables and health-seeking behaviour of patients using public and private hospitals.FindingsThe results showed that there is a significant relationship between the socio-demographic characteristics (sex, marital status, education, level of income) and the health-seeking behaviour of patients in regard to the utilisation of public and private health facilities (p < 0.000).Originality/valueThere is a significant relationship between patients' socio-demographic variables and their choice and utilisation of public and private healthcare services. This information is of value to policy makers so that they have an idea on the socio-demographic behavioural variables that influence patients' health-seeking behaviour.

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Insulin suppresses IKs (KCNQ1/KCNE1) currents, which require β-subunit KCNE1

Obara

Norota

et al. 2013

Pflugers Arch - Eur J Physiol

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Abnormal QT prolongation in diabetic patients has become a clinical problem because it increases the risk of lethal ventricular arrhythmia. In an animal model of type 1 diabetes mellitus, several ion currents, including the slowly activating delayed rectifier potassium current (IKs), are altered. The IKs channel is composed of KCNQ1 and KCNE1 subunits, whose genetic mutations are well known to cause long QT syndrome. Although insulin is known to affect many physiological and pathophysiological events in the heart, acute effects of insulin on cardiac ion channels are poorly understood at present. This study was designed to investigate direct electrophysiological effects of insulin on IKs (KCNQ1/KCNE1) currents. KCNQ1 and KCNE1 were co-expressed in Xenopus oocytes, and whole cell currents were measured by a two-microelectrode voltage-clamp method. Acute application of insulin suppressed the KCNQ1/KCNE1 currents and phosphorylated Akt and extracellular signal-regulated kinase (ERK), the two major downstream effectors, in a concentration-dependent manner. Wortmannin (10(-6) M), a phosphoinositide 3-kinase (PI3K) inhibitor, attenuated the suppression of the currents and phosphorylation of Akt by insulin, whereas U0126 (10(-5) M), a mitogen-activated protein kinase kinase (MEK) inhibitor, had no effect on insulin-induced suppression of the currents. In addition, insulin had little effect on KCNQ1 currents without KCNE1, which indicated an essential role of KCNE1 in the acute suppressive effects of insulin. Mutagenesis studies revealed amino acid residues 111-118 within the distal third C-terminus of KCNE1 as an important region. Insulin has direct electrophysiological effects on IKs currents, which may affect cardiac excitability.

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The role of acute hyperinsulinemia in the development of cardiac arrhythmias

Cited by 5 publications

References 34 publications

Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes

Exome Analyses of Long QT Syndrome Reveal Candidate Pathogenic Mutations in Calmodulin-Interacting Genes

The influence of sociodemographic behavioural variables on health-seeking behaviour and the utilisation of public and private hospitals in Ghana

Insulin suppresses IKs (KCNQ1/KCNE1) currents, which require β-subunit KCNE1

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