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Hyperglycemia-induced cardiac contractile dysfunction in the diabetic heart

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Abstract

The development of a diabetic cardiomyopathy is a multifactorial process, and evidence is accumulating that defects in intracellular free calcium concentration [Ca2+]i or its homeostasis are related to impaired mechanical performance of the diabetic heart leading to a reduction in contractile dysfunction. Defects in ryanodine receptor, reduced activity of the sarcoplasmic reticulum calcium pump (SERCA) and, along with reduced activity of the sodium-calcium exchanger (NCX) and alterations in myofilament, collectively cause a calcium imbalance within the diabetic cardiomyocytes. This in turn is characterized by cytosolic calcium overloading or elevated diastolic calcium leading to heart failure. Numerous studies have been performed to identify the cellular, subcellular, and molecular derangements in diabetes-induced cardiomyopathy (DCM), but the precise mechanism(s) is still unknown. This review focuses on the mechanism behind DCM, the onset of contractile dysfunction, and the associated changes with special emphasis on hyperglycemia, mitochondrial dysfunction in the diabetic heart. Further, management strategies, including treatment and emerging therapeutic modalities, are discussed.

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Authors and Affiliations

  1. School of Forensic and Applied Sciences, University of Central Lancashire, Preston, England, PR1 2HE, UK

    Raphael M. Singh, Tahreem Waqar & Jaipaul Singh

  2. Faculty of Medicine and Health Sciences, University of Guyana, Turkeyen, Georgetown, Guyana

    Raphael M. Singh

  3. Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

    Frank C. Howarth

  4. Department of Human Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

    Ernest Adeghate

  5. Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Centre, Omaha, NE, 68198, USA

    Keshore Bidasee

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Singh, R.M., Waqar, T., Howarth, F.C. et al. Hyperglycemia-induced cardiac contractile dysfunction in the diabetic heart. Heart Fail Rev 23, 37–54 (2018). https://doi.org/10.1007/s10741-017-9663-y

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