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Publication

The absence of insulin signaling in the heart induces changes in potassium channel expression and ventricular repolarization.

Authors Lopez-Izquierdo A, Pereira RO, Wende AR, Punske BB, Abel ED, Tristani-Firouzi M Submitted By Submitted Externally on 3/4/2015 Status Published Journal American journal of physiology. Heart and circulatory physiology Year 2014 Date Published 3/1/2014 Volume : Pages 306 : H747 - H754 PubMed Reference 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.

Investigators with authorship
Name Institution E. Dale Abel University of Iowa Adam Wende University of Alabama at Birmingham

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