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Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review

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Abstract

Diabetes mellitus is one of the most common chronic diseases affecting millions of people worldwide. Cardiovascular complication including myocardial infarction is one of the major causes of death in diabetic patients. Diabetes mellitus induces abnormal pathological findings including cell hypertrophy, neuropathy, interstitial fibrosis, myocytolysis and apoptosis and lipid deposits in the heart. In addition, the cytoplasmic organelles of cardiomyocytes including the plasma membrane, mitochondrion and sarcoplasmic reticulum are also impaired in both type I and type II diabetes. Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy in patients suffering from diabetes. Hyperglycaemia promotes the production of reactive oxygen (ROS) and nitrogen species (RNS). The release of ROS and RNS induces oxidative stress leading to abnormal gene expression, faulty signal transduction and apoptosis of cardiomyocytes. Hyperglycaemia also induces apoptosis by p53 and the activation of the cytochrome c-activated caspase-3 pathway. Stimulation of connective tissue growth factor and the formation of advanced glycation end products in extracellular matrix proteins induces collagen cross-linking and contribute to the fibrosis observed in the interstitium of the heart of diabetic subjects. In terms of signal transduction, defects in intracellular Ca2+ signalling due to alteration of expression and function of proteins that regulate intracellular Ca2+ also occur in diabetes. All of these abnormalities result in gross dysfunction of the heart. Beta-adrenoreceptor antagonists, ACE inhibitors, endothelin-receptor antagonist (Bonestan®), adrenomedullin, hormones (insulin, IGF-1) and antioxidants (magniferin, metallothionein, vitamins C and E) reduce interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy. (Mol Cell Biochem 261: 187–191, 2004)

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  1. Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

    Ernest Adeghate

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Adeghate, E. Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review. Mol Cell Biochem 261, 187–191 (2004). https://doi.org/10.1023/B:MCBI.0000028755.86521.11

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  • DOI: https://doi.org/10.1023/B:MCBI.0000028755.86521.11

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