Effects of diabetes-induced hyperglycemia in the heart: Biochemical and structural alterations

Tahreem Iqbal, Philip J. Welsby, Frank C. Howarth, Keshore Bidasee, Ernest Adeghate, Jaipaul Singh

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Hyperglycemia (HG) plays a major role in the development of diabetes mellitus (DM) and its complications. HG induces numerous maladaptations at the cellular level and moreover it is an independent risk factor to worsen cardiac performance and cell survival. The heart is a major target organ for damage with hyperglycemia. Alterations as a result of HG can lead to the development of a diabetic cardiomyopathy, resulting in changes to cardiac structure and function. Mechanisms damaging the heart are similar to those that damage the vasculature, but are more widespread in the myocardium. Four major pathways are implicated in HG-induced cardiac and vascular damage, including increases in advanced glycation end products (AGEs), enhanced hexosamine and polyol fl ux, and activation of classical isoforms of protein kinase C (PKC). These changes lead to abnormalities such as increased ventricular stiffness, cardiac fi brosis, derangement in cellular calcium ion homeostasis, and reduced myocyte contractility, resulting in heart failure (HF) over time. These pathways refl ect upon a single HG-induced process of overproduction of superoxide by the mitochondrial electron-transport chain, which is responsible for the changes occurring in the heart. This chapter discusses the HG-induced pathways, focusing on their effects on the structure of the diabetic heart, as well as examining the downstream signaling whereby oxidative stress leads to myocardial fi brosis and impaired contractile function. In addition, this review highlights the role of endothelin-1 (ET-1) in endothelial dysfunction and the effects of humoral factors, angiotensin II and transforming growth factor-ß, in evoking multiple signaling pathways in cardiac fi broblasts or fi brosis that leads to cardiac remodelling. How these signaling pathways mediated by HG contribute to the pathophysiological alterations in the heart is also discussed in this review.

Original languageEnglish (US)
Title of host publicationDiabetic Cardiomyopathy
Subtitle of host publicationBiochemical and Molecular Mechanisms
PublisherSpringer New York
Pages77-106
Number of pages30
ISBN (Electronic)9781461493174
ISBN (Print)9781461493167
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Cardiac remodelling
  • Diabetes mellitus
  • Diabetic cardiomyopathy
  • Endothelial cell dysfunction
  • Heart structure
  • Hyperglycemia
  • Signaling pathways

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Iqbal, T., Welsby, P. J., Howarth, F. C., Bidasee, K., Adeghate, E., & Singh, J. (2014). Effects of diabetes-induced hyperglycemia in the heart: Biochemical and structural alterations. In Diabetic Cardiomyopathy: Biochemical and Molecular Mechanisms (pp. 77-106). Springer New York. https://doi.org/10.1007/978-1-4614-9317-4_5