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 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 (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
E. Dale AbelUniversity of Iowa
Adam WendeUniversity of Alabama at Birmingham