Cardiovascular action of insulin in health and disease: endothelial L-arginine transport and cardiac voltage-dependent potassium channels

Dubo, Sebastian, Gallegos, David, Cabrera, Lissette, Sobrevia, Luis, Zuniga, Leandro and Gonzalez, Marcelo (2016) Cardiovascular action of insulin in health and disease: endothelial L-arginine transport and cardiac voltage-dependent potassium channels. Frontiers in Physiology, 7 . doi:10.3389/fphys.2016.00074


Author Dubo, Sebastian
Gallegos, David
Cabrera, Lissette
Sobrevia, Luis
Zuniga, Leandro
Gonzalez, Marcelo
Title Cardiovascular action of insulin in health and disease: endothelial L-arginine transport and cardiac voltage-dependent potassium channels
Journal name Frontiers in Physiology   Check publisher's open access policy
ISSN 1664-042X
Publication date 2016-03-15
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.3389/fphys.2016.00074
Open Access Status DOI
Volume 7
Total pages 19
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2017
Language eng
Formatted abstract
Impairment of insulin signaling on diabetes mellitus has been related to cardiovascular dysfunction, heart failure, and sudden death. In human endothelium, cationic amino acid transporter 1 (hCAT-1) is related to the synthesis of nitric oxide (NO) and insulin has a vascular effect in endothelial cells through a signaling pathway that involves increases in hCAT-1 expression and L-arginine transport. This mechanism is disrupted in diabetes, a phenomenon potentiated by excessive accumulation of reactive oxygen species (ROS), which contribute to lower availability of NO and endothelial dysfunction. On the other hand, electrical remodeling in cardiomyocytes is considered a key factor in heart failure progression associated to diabetes mellitus. This generates a challenge to understand the specific role of insulin and the pathways involved in cardiac function. Studies on isolated mammalian cardiomyocytes have shown prolongated action potential in ventricular repolarization phase that produces a long QT interval, which is well explained by attenuation in the repolarizing potassium currents in cardiac ventricles. Impaired insulin signaling causes specific changes in these currents, such a decrease amplitude of the transient outward K+ (Ito) and the ultra-rapid delayed rectifier (IKur) currents where, together, a reduction of mRNA and protein expression levels of a-subunits (Ito, fast; Kv 4.2 and IKs; Kv 1.5) or β-subunits (KChIP2 and MiRP) of K+ channels involved in these currents in a MAPK mediated pathway process have been described. These results support the hypothesis that lack of insulin signaling can produce an abnormal repolarization in cardiomyocytes. Furthermore, the arrhythmogenic potential due to reduced Ito current can contribute to an increase in the incidence of sudden death in heart failure. This review aims to show, based on pathophysiological models, the regulatory function that would have insulin in vascular system and in cardiac electrophysiology.
Keyword Insulin
L-arginine
Nitric oxide
Endothelium
Cardiac potassium channels
Ventricular repolarization
Heart failure
Insulin resistance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
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