Journal article
Substrate-Specific Derangements in Mitochondrial Metabolism and Redox Balance in the Atrium of the Type 2 Diabetic Human Heart
Journal of the American College of Cardiology, Vol.54(20), pp.1891-1898
11/10/2009
DOI: 10.1016/j.jacc.2009.07.031
PMCID: PMC2800130
PMID: 19892241
Abstract
The aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients.
Heart failure represents a major cause of death among diabetic patients. It has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this comorbidity, but scarce evidence exists in support of this mechanism in humans.
Mitochondrial oxygen (O2) consumption and hydrogen peroxide (H2O2) emission were measured in permeabilized myofibers prepared from samples of the right atrial appendage obtained from nondiabetic (n = 13) and diabetic (n = 11) patients undergoing nonemergent coronary artery bypass graft surgery.
Mitochondria in atrial tissue of type 2 diabetic individuals show a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to nondiabetic patients. Furthermore, diabetic patients show an increased mitochondrial H2O2emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue.
These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they show that mitochondria in diabetic human hearts have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H2O2emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients.
Details
- Title: Subtitle
- Substrate-Specific Derangements in Mitochondrial Metabolism and Redox Balance in the Atrium of the Type 2 Diabetic Human Heart
- Creators
- Ethan J Anderson - Department of Cardiovascular Sciences and East Carolina Heart Institute, East Carolina University, Greenville, North CarolinaAlan P Kypson - Department of Cardiovascular Sciences and East Carolina Heart Institute, East Carolina University, Greenville, North CarolinaEvelio Rodriguez - Department of Cardiovascular Sciences and East Carolina Heart Institute, East Carolina University, Greenville, North CarolinaCurtis A Anderson - Department of Cardiovascular Sciences and East Carolina Heart Institute, East Carolina University, Greenville, North CarolinaEric J Lehr - Department of Cardiovascular Sciences and East Carolina Heart Institute, East Carolina University, Greenville, North CarolinaP. Darrell Neufer - Metabolic Institute for the Study of Diabetes and Obesity, East Carolina University, Greenville, North Carolina
- Resource Type
- Journal article
- Publication Details
- Journal of the American College of Cardiology, Vol.54(20), pp.1891-1898
- DOI
- 10.1016/j.jacc.2009.07.031
- PMID
- 19892241
- PMCID
- PMC2800130
- NLM abbreviation
- J Am Coll Cardiol
- ISSN
- 0735-1097
- eISSN
- 1558-3597
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/10/2009
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984065693502771
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