Heart Failure Reviews

, Volume 19, Issue 1, pp 87–99 | Cite as

Mechanisms of subcellular remodeling in heart failure due to diabetes

  • Naranjan S. DhallaEmail author
  • Nobuakira Takeda
  • Delfin Rodriguez-Leyva
  • Vijayan Elimban


Diabetic cardiomyopathy is not only associated with heart failure but there also occurs a loss of the positive inotropic effect of different agents. It is now becoming clear that cardiac dysfunction in chronic diabetes is intimately involved with Ca2+-handling abnormalities, metabolic defects and impaired sensitivity of myofibrils to Ca2+ in cardiomyocytes. On the other hand, loss of the inotropic effect in diabetic myocardium is elicited by changes in signal transduction mechanisms involving hormone receptors and depressions in phosphorylation of various membrane proteins. Ca2+-handling abnormalities in the diabetic heart occur mainly due to defects in sarcolemmal Na+–K+ ATPase, Na+–Ca2+ exchange, Na+–H+ exchange, Ca2+-channels and Ca2+-pump activities as well as changes in sarcoplasmic reticular Ca2+-uptake and Ca2+-release processes; these alterations may lead to the occurrence of intracellular Ca2+ overload. Metabolic defects due to insulin deficiency or ineffectiveness as well as hormone imbalance in diabetes are primarily associated with a shift in substrate utilization and changes in the oxidation of fatty acids in cardiomyocytes. Mitochondria initially seem to play an adaptive role in serving as a Ca2+ sink, but the excessive utilization of long-chain fatty acids for a prolonged period results in the generation of oxidative stress and impairment of their function in the diabetic heart. In view of the activation of sympathetic nervous system and renin-angiotensin system as well as platelet aggregation, endothelial dysfunction and generation of oxidative stress in diabetes and blockade of their effects have been shown to attenuate subcellular remodeling, metabolic derangements and signal transduction abnormalities in the diabetic heart. On the basis of these observations, it is suggested that oxidative stress and subcellular remodeling due to hormonal imbalance and metabolic defects play a critical role in the genesis of heart failure during the development of diabetic cardiomyopathy.


Sarcolemmal defects Ca2+-handling abnormalities Sarcoplasmic reticular defects Myofibrillar proteins Mitochondrial function Subcellular remodeling 



The infrastructure support for the work in this article was provided by the St. Boniface Hospital Research Foundation.

Conflict of interest

The authors have no conflict of interest with any funding agency.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Naranjan S. Dhalla
    • 1
    Email author
  • Nobuakira Takeda
    • 2
  • Delfin Rodriguez-Leyva
    • 3
  • Vijayan Elimban
    • 1
  1. 1.Department of Physiology, Faculty of Medicine, Institute of Cardiovascular Sciences, St. Boniface Hospital ResearchUniversity of ManitobaWinnipegCanada
  2. 2.Department of Internal Medicine, Katsushika Medical CentreJikei UniversityTokyoJapan
  3. 3.Holguin University HospitalHolguinCuba

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