ReviewAntioxidants (Basel, Switzerland)2023
Inhibition of Pyruvate Dehydrogenase in the Heart as an Initiating Event in the Development of Diabetic Cardiomyopathy.
Review in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- RND3 Enhances Cardiac Glucose Metabolism Through Inhibiting ACAT1-Dependent PDHA1 Acetylation and Protects Against Ischemia-Reperfusion Injury.Circulation · 2026Article
- Sirtuins at the Interface of Glucose Metabolism, Diabetes, and Heart Failure: Metabolic Sensing in Cardiometabolic Disease.International journal of molecular sciences · 2026Review
- Biomarkers of Cardiac Metabolic Flexibility in Health, HFrEF and HFpEF.International journal of molecular sciences · 2026Review
- Systemic effects of type 2 diabetes therapies: an integrated perspective on the cardio-renal- cerebral-metabolic axis.Frontiers in medicine · 2026Review
- Metabolomic Biomarkers for Non-Invasive Diagnosis of Coronary Artery Disease and Obstructive Sleep Apnea Co-Occurrence.Nature and science of sleep · 2026Article
- PFKFB2 Is Pivotal for Metabolic Flexibility and Differential Glucose Utilization.Journal of the American Heart Association · 2025Article
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Spatial profiling of carbonyl metabolites in diabetic cardiomyopathy by derivatization-assisted ambient mass spectrometry imaging.Analytical and bioanalytical chemistry · 2025Article
- Reciprocal rescue of Wolfram syndrome by two causative genes.EMBO reports · 2025Article
- Molecular Targets and Small Molecules Modulating Acetyl Coenzyme A in Physiology and Diseases.ACS pharmacology & translational science · 2025Review
- MCU genetically altered mice suggest how mitochondrial CaTrends in endocrinology and metabolism: TEM · 2024Review
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- Review
- Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart.Journal of the American Heart Association · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Obesity affects a growing fraction of the population and is a risk factor for type 2 diabetes and cardiovascular disease. Even in the absence of hypertension and coronary artery disease, type 2 diabetes can result in a heart disease termed diabetic cardiomyopathy. Diminished glucose oxidation, increased reliance on fatty acid oxidation for energy production, and oxidative stress are believed to play causal roles. However, the progression of metabolic changes and mechanisms by which these changes impact the heart have not been established. Cardiac pyruvate dehydrogenase (PDH), the central regulatory site for glucose oxidation, is rapidly inhibited in mice fed high dietary fat, a model of obesity and diabetes. Increased reliance on fatty acid oxidation for energy production, in turn, enhances mitochondrial pro-oxidant production. Inhibition of PDH may therefore initiate metabolic inflexibility and oxidative stress and precipitate diabetic cardiomyopathy. We discuss evidence from the literature that supports a role for PDH inhibition in loss in energy homeostasis and diastolic function in obese and diabetic humans and in rodent models. Finally, seemingly contradictory findings highlight the complexity of the disease and the need to delineate progressive changes in cardiac metabolism, the impact on myocardial structure and function, and the ability to intercede.
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Registered trials
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