Loss of insulin signaling may contribute to atrial fibrillation and atrial electrical remodeling in type 1 diabetes

Significance Atrial fibrillation (AF) is prevalent in diabetic patients, yet the basis for AF in diabetes is poorly understood. We have used type 1 diabetic Akita mice to study the effects of insulin on atrial electrophysiology in diabetes. We demonstrate that Akita mice are highly susceptible to AF due to impaired electrical conduction and that insulin treatment can reduce the occurrence of this arrhythmia. Atrial action potential morphology was altered in Akita mice in association with reductions in atrial Na + current (I Na ) and repolarizing potassium current. Insulin treatment potently increased atrial I Na via distinct chronic and acute effects. These experiments identify antiarrhythmic effects of insulin in type 1 diabetes via potent effects on atrial I Na .