ArticleAmerican journal of physiology. Heart and circulatory physiology2014
The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes.Clinical research in cardiology : official journal of the German Cardiac Society · 2022Trial
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke.Translational stroke research · 2025Article
- Immune cells and arrhythmias.Cardiovascular research · 2025Review
- Insulin mitigates acute ischemia-induced atrial fibrillation and sinoatrial node dysfunction ex vivo.JCI insight · 2024Article
- In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation.Cardiovascular diabetology · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- The Association between the Differential Expression of lncRNA and Type 2 Diabetes Mellitus in People with Hypertriglyceridemia.International journal of molecular sciences · 2023Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Two-hit mechanism of cardiac arrhythmias in diabetic hyperglycaemia: reduced repolarization reserve, neurohormonal stimulation, and heart failure exacerbate susceptibility.Cardiovascular research · 2021Article
- Insulin action at a molecular level - 100 years of progress.Molecular metabolism · 2021Review
- Insulin signaling in the heart.American journal of physiology. Endocrinology and metabolism · 2021Review
- Isolated downregulation of HCN2 in ventricles of rats with streptozotocin-induced diabetic cardiomyopathy.BMC cardiovascular disorders · 2021Article
- Diabetes-induced changes in cardiac voltage-gated ion channels.World journal of diabetes · 2021Review
- Multiple daily insulin injections ameliorate QT interval by lowering blood glucose levels in patients with type 2 diabetes.Therapeutic advances in endocrinology and metabolism · 2021Article
- Atrial remodeling and atrial fibrillation in acquired forms of cardiovascular disease.Heart rhythm O2 · 2020Article
- The Pathogenic Role of Very Low Density Lipoprotein on Atrial Remodeling in the Metabolic Syndrome.International journal of molecular sciences · 2020Review
- The Association Between Diabetes Mellitus and Atrial Fibrillation: Clinical and Mechanistic Insights.Frontiers in physiology · 2019Review
- Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects.Cardiology and therapy · 2019Article
- Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Diabetes mellitus increases the risk for cardiac dysfunction, heart failure, and sudden death. The wide array of neurohumoral changes associated with diabetes pose a challenge to understanding the roles of specific pathways that alter cardiac function. Here, we use a mouse model with cardiomyocyte-restricted deletion of insulin receptors (CIRKO, cardiac-specific insulin receptor knockout) to study the specific effects of impaired cardiac insulin signaling on ventricular repolarization, independent of the generalized metabolic derangements associated with diabetes. Impaired insulin action caused a reduction in mRNA and protein expression of several key K(+) channels that dominate ventricular repolarization. Specifically, components of transient outward K(+) current fast component (Ito,fast; Kv4.2 and KChiP2) were reduced, consistent with a reduction in the amplitude of Ito,fast in isolated left ventricular CIRKO myocytes, compared with littermate controls. The reduction in Ito,fast resulted in ventricular action potential prolongation and prolongation of the QT interval on the surface ECG. These results support the notion that the lack of insulin signaling in the heart is sufficient to cause the repolarization abnormalities described in other animal models of diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.