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Diabetes mellitus attenuates the repolarization reserve in mammalian heart.
Cardiovasc Res ; 73(3): 512-20, 2007 Feb 01.
Article in En | MEDLINE | ID: mdl-17182020
ABSTRACT

OBJECTIVE:

In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts. METHODS AND

RESULTS:

Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially diminished by insulin.

CONCLUSION:

It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing I(to) and I(Ks) currents, and thereby may markedly enhance the risk of sudden cardiac death.
Subject(s)
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Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 1 / Myocardium Limits: Animals Language: En Journal: Cardiovasc Res Year: 2007 Document type: Article Affiliation country: Hungria
Search on Google
Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 1 / Myocardium Limits: Animals Language: En Journal: Cardiovasc Res Year: 2007 Document type: Article Affiliation country: Hungria
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