NOD Mice Recapitulate the Cardiac Disturbances Observed in Type 1 Diabetes

J Cardiovasc Transl Res. 2021 Apr;14(2):271-282. doi: 10.1007/s12265-020-10039-y. Epub 2020 May 28.

Abstract

This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac function was evaluated by echocardiography and electrocardiography (ECG). Action potentials (AP) and Ca2+ transients were evaluated at whole heart level. Heart mitochondrial function was evaluated by high-resolution respirometry and H2O2 release. NOD mice presented a reduction in hearth weight. Mitochondrial oxygen fluxes and H2O2 release were similar between NOD and NOR mice. ECG revealed a QJ interval prolongation in NOD mice. Furthermore, AP duration at 30% of repolarization was increased, and it depicted slower Ca2+ transient kinetics. NOD mice presented greater number/severity of ventricular arrhythmias both in vivo and in vitro. In conclusion, NOD mice evoked cardiac electrical and calcium handling disturbances similar to the observed in T1D. Graphical Abstract .

Keywords: Arrhythmias; Electrophysiology; Mitochondria; NOD mice; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Animals
  • Arrhythmias, Cardiac / etiology*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Blood Glucose / metabolism*
  • Calcium Signaling*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Disease Models, Animal
  • Heart Conduction System / metabolism*
  • Heart Conduction System / physiopathology
  • Heart Rate*
  • Kinetics
  • Mice
  • Mice, Inbred NOD
  • Mitochondria, Heart / metabolism
  • Myocytes, Cardiac / metabolism*

Substances

  • Blood Glucose