Diabetes abolish cardioprotective effects of remote ischemic conditioning: evidences and possible mechanisms

  • Sakshi Tyagi
  • Nirmal Singh
  • Jasleen kaur Virdi
  • Amteshwar Singh JaggiEmail author


Diabetes mellitus significantly hampers the development of cardioprotective response to remote pre/post/perconditioning stimuli by impairing the activation of cardioprotective signaling pathways. Among the different pathways, the impairment in O-linked β-N-acetylglucosamine (O-GlcNAc) signaling and release of cardioprotective humoral factor may contribute in attenuating remote preconditioning-induced cardioprotection. Moreover, the failure to phosphorylate extracellular signal related kinase (ERK), phosphoinositide-3-kinase (PI3K), and AKT along with up-regulation of mechanistic target of rapamycin (mTOR) and decrease in autophagy may also attenuate remote preconditioning-induced cardioprotection. Remote perconditioning stimulus also fails to phosphorylate AKT kinase in diabetic heart. In addition, diabetes may increase the oxidative stress, reactive oxygen species (ROS) production, decrease the beclin expression, and inhibit autophagy to attenuate remote perconditioning-induced cardioprotection. Moreover, diabetes-induced increase in the Rho-associated kinase (ROCK) activity, decrease in the arginase activity, and reduction in nitric oxide (NO) bioavailability may also contribute in decreasing remote perconditioning-induced cardioprotection. Diabetes may reduce the phosphorylation of adenosine 5′-monophosphate activated protein kinase (AMPKα) and increase the phosphorylation of mTOR to attenuate cardioprotection of remote postconditioning. The present review describes the role of diabetes in attenuating remote ischemic conditioning-induced cardioprotection along with the possible mechanisms.


Oxidative stress Heart Diabetes Autophagy ROCK 



The authors are thankful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India for supporting the study.

Compliance with ethical standards

Disclosure of potential conflicts of interest

The authors declare no conflict of interests.

Research involving human participants and/or animals

The study did not involve usage of animals or employment of human participants.

Informed consent

The study did not involve participants of human volunteers.


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© University of Navarra 2019

Authors and Affiliations

  • Sakshi Tyagi
    • 1
  • Nirmal Singh
    • 1
  • Jasleen kaur Virdi
    • 1
  • Amteshwar Singh Jaggi
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences and Drug ResearchPunjabi UniversityPatialaIndia

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