Cyanocobalamin prevents cardiomyopathy in type 1 diabetes by modulating oxidative stress and DNMT-SOCS1/3-IGF-1 signaling

Commun Biol. 2021 Jun 23;4(1):775. doi: 10.1038/s42003-021-02291-y.


Patients with long-standing diabetes have a high risk for cardiac complications that is exacerbated by increased reactive oxygen species (ROS) production. We found that feeding cyanocobalamin (B12), a scavenger of superoxide, not only prevented but reversed signs of cardiomyopathy in type 1 diabetic Elmo1H/H Ins2Akita/+ mice. ROS reductions in plasma and hearts were comparable to those in mice treated with other antioxidants, N-acetyl-L-cysteine or tempol, but B12 produced better cardioprotective effects. Diabetes markedly decreased plasma insulin-like growth factor (IGF)-1 levels, while B12, but not N-acetyl-L-cysteine nor tempol, restored them. B12 activated hepatic IGF-1 production via normalization of S-adenosylmethionine levels, DNA methyltransferase (DNMT)-1/3a/3b mRNA, and DNA methylation of promoters for suppressor of cytokine signaling (SOCS)-1/3. Reductions of cardiac IGF-1 mRNA and phosphorylated IGF-1 receptors were also restored. Thus, B12 is a promising option for preventing diabetic cardiomyopathy via ROS reduction and IGF-1 retrieval through DNMT-SOCS1/3 signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Cardiomyopathies / prevention & control*
  • DNA-Cytosine Methylases / physiology*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / metabolism
  • Female
  • Insulin-Like Growth Factor I / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects*
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling 1 Protein / physiology*
  • Suppressor of Cytokine Signaling 3 Protein / physiology*
  • Vitamin B 12 / pharmacology*


  • Adaptor Proteins, Signal Transducing
  • ELMO1 protein, mouse
  • Socs1 protein, mouse
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I
  • DNA-Cytosine Methylases
  • Vitamin B 12