Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1 beta, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1 beta and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2+ teak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1 beta mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca2+ leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

The study demonstrates that type 2 diabetes mice have an increased risk of arrhythmia, mainly due to the increased SR Ca2+ leak caused by cardiac IL-1β-mediated mitoROS generation. Inhibiting IL-1β and mitoROS can reduce the risk of arrhythmias. Reversing diabetic arrhythmia can be achieved by stabilizing the RyR2 channel.