Journal article
The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization
American journal of physiology. Heart and circulatory physiology, Vol.306(5), pp.H747-H754
03/01/2014
DOI: 10.1152/ajpheart.00849.2013
PMCID: PMC3949065
PMID: 24375641
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 (
I
to,fast
; Kv4.2 and KChiP2) were reduced, consistent with a reduction in the amplitude of
I
to,fast
in isolated left ventricular CIRKO myocytes, compared with littermate controls. The reduction in
I
to,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.
Details
- Title: Subtitle
- The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization
- Creators
- Angelica Lopez-Izquierdo - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UtahRenata O Pereira - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, UtahAdam R Wende - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, UtahBonnie B Punske - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UtahE. Dale Abel - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, UtahMartin Tristani-Firouzi - Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.306(5), pp.H747-H754
- DOI
- 10.1152/ajpheart.00849.2013
- PMID
- 24375641
- PMCID
- PMC3949065
- NLM abbreviation
- Am J Physiol Heart Circ Physiol
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Publisher
- American Physiological Society; Bethesda, MD
- Language
- English
- Date published
- 03/01/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024511002771
Metrics
11 Record Views