Insulin Similar to Activator of KCNQ1 Channel Recovers the Prolonged Repolarization of Ventricular Cardiomyocytes from Insulin Resistant Aged Rats

Abstract

Both cardiac dysfunction and systemic insulin resistance mostly observed together with advancing aging or metabolic syndrome (MetS), while the exact underlying mechanisms of heart‐specific insulin resistance and cardiac dysfunction still remain unclear. There also are relations between delayed ventricular repolarization, increased risk in arrhythmia and QT‐prolongation in ECG with diabetes, aging and MetS. They also showed that the mutations/functional alterations in QT‐prolongation related K+‐channels such as KCNQ1‐channels might be responsible for these changes. In addition, most of recent observations that insulin sensitivity of glucose metabolism are affected by a new molecule KCNQ1, which brings up a thought on possible relation of development of insulin resistance, changes in this channel and QT‐prolongations in senescent mammalian cardiomyocytes. Therefore, we aimed to clarify a possible association between prolonged action potential duration and alterations in KCNQ1‐channel function as well as insulin application in ventricular cardiomyocytes from either insulin resistant aged or MetS rats. Our data showed that there is a significant prolongation in action potential repolarization phase in isolated cardiomyocytes from insulin‐resistant aged or MetS rats, while those animals have a significant prolonged‐QT in ECG and can respond to insulin application. Besides, application of KCNQ1‐channel activator reduced the prolonged action potential repolarizations and this indicates the contribution of KCNQ1‐currents and possible benefits of insulin on action potential prolongation of both aged and MetS cardiomyocytes. Our present study also showed that the protein expression level of KCNQ1 and KCNE1 remained unchanged. Overall, our present results can reveal important information on the contributions of these parameters on the aging‐related or metabolic syndrome‐related cardiac dysfunction and the effect of insulin on these alterations. Therefore, our findings will contribute to the literature and the clinical applications with a new therapeutic approach by revealing the molecular mechanisms of insulin treatment on insulin resistant aged or MetS mammalian cardiac dysfunction.Support or Funding InformationSupported through TUBITAK SBAG‐119S661