Diabetes-related metabolic perturbations in cardiac myocyte

Diabetes Metab. 2008 Feb:34 Suppl 1:S3-9. doi: 10.1016/S1262-3636(08)70096-X.

Abstract

Although the pathogenesis of diabetic cardiomyopathy is poorly understood, recent evidence implicates perturbations in cardiac energy metabolism. Whereas mitochondrial fatty acid oxidation is the chief energy source for the normal postnatal mammalian heart, the relative contribution of glucose utilization pathways is significant, allowing the plasticity necessary for steady ATP production in the context of diverse physiologic and dietary conditions. In the uncontrolled diabetic state, because of the combined effects of insulin resistance and high circulating fatty acids, cardiac myocytes use fatty acids almost exclusively to support ATP synthesis. Studies using various diabetic rodent models have shown a direct relationship between the chronic drive on myocardial fatty acid metabolism and the development of cardiomyopathy including ventricular hypertrophy and dysfunction. Fatty acids also play a critical role in triggering the development of cellular insulin resistance through derangements in insulin signalling cascade. There are similarities in cardiac dysfunction in animal models and human type 2 diabetes and/or obesity. For instance, obese young women showed increased cardiac fatty acid utilization measured by positron emission tomography and increased myocardial oxygen consumption with reduced cardiac efficiency. Furthermore, accumulation of triglycerides within cardiac myocytes was an early metabolic marker that was associated with increased left ventricular mass. Moreover, data indicate that alterations in cardiac energetics occur early in the pathophysiology of type 2 diabetes and are correlated negatively with the fasting plasma free fatty acid concentrations.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Angiopathies / metabolism*
  • Energy Metabolism
  • Humans
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • Myocytes, Cardiac / metabolism*
  • Reference Values