ArticleAmerican journal of physiology. Heart and circulatory physiology2021
Why the diabetic heart is energy inefficient: a ketogenesis and ketolysis perspective.
Article in American journal of physiology. Heart and circulatory physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Empagliflozin improves metabolism and prevents myocardial and coronary dysfunction in streptozotocin-diabetic and non-diabetic rats subjected to ischemia/reperfusion.Basic research in cardiology · 2026Article
- Metabolic syndrome and a broken heart: trust your gut or risk your heart.American journal of physiology. Heart and circulatory physiology · 2026Review
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- Characteristics of Cardiac Ketone Body Metabolism Throughout the Life Cycle.Cardiovascular therapeutics · 2025Review
- Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond.Cardiovascular research · 2024Review
- Recent advances associated with cardiometabolic remodeling in diabetes-induced heart failure.American journal of physiology. Heart and circulatory physiology · 2024Review
- Regulation of cardiac ferroptosis in diabetic human heart failure: uncovering molecular pathways and key targets.Cell death discovery · 2024Article
- Empagliflozin improves mitochondrial dysfunction in diabetic cardiomyopathy by modulating ketone body metabolism and oxidative stress.Redox biology · 2024Article
- Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555.International journal of molecular sciences · 2024Article
- Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy.Frontiers in cardiovascular medicine · 2024Review
- Ironing out the details: ferroptosis and its relevance to diabetic cardiomyopathy.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Review
- Impact of Prenatal Exposure to Maternal Diabetes and High-Fat Diet on Postnatal Myocardial Ketone Body Metabolism in Rats.International journal of molecular sciences · 2023Article
- Ketone Bodies and Cardiovascular Disease: An Alternate Fuel Source to the Rescue.International journal of molecular sciences · 2023Review
- Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis.Journal of translational medicine · 2023Article
- Guidelines on models of diabetic heart disease.American journal of physiology. Heart and circulatory physiology · 2022Review
- A 90-Day Safety Study of Meat fromLife (Basel, Switzerland) · 2022Article
- Metabolites and Genes behind Cardiac Metabolic Remodeling in Mice with Type 1 Diabetes Mellitus.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Lack of glucose uptake compromises metabolic flexibility and reduces energy efficiency in the diabetes mellitus (DM) heart. Although increased use of fatty acid to compensate glucose substrate has been studied, less is known about ketone body metabolism in the DM heart. Ketogenic diet reduces obesity, a risk factor for T2DM. How ketogenic diet affects ketone metabolism in the DM heart remains unclear. At the metabolic level, the DM heart differs from the non-DM heart because of altered metabolic substrate and the T1DM heart differs from the T2DM heart because of insulin levels. How these changes affect ketone body metabolism in the DM heart are poorly understood. Ketogenesis produces ketone bodies by using acetyl-CoA, whereas ketolysis consumes ketone bodies to produce acetyl-CoA, showing their opposite roles in the ketone body metabolism. Cardiac-specific transgenic upregulation of ketogenesis enzyme or knockout of ketolysis enzyme causes metabolic abnormalities leading to cardiac dysfunction. Empirical evidence demonstrates upregulated transcription of ketogenesis enzymes, no change in the levels of ketone body transporters, very high levels of ketone bodies, and reduced expression and activity of ketolysis enzymes in the T1DM heart. Based on these observations, I hypothesize that increased transcription and activity of cardiac ketogenesis enzyme suppresses ketolysis enzyme in the DM heart, which decreases cardiac energy efficiency. The T1DM heart exhibits highly upregulated ketogenesis compared with the T2DM heart because of the lack of insulin, which inhibits ketogenesis enzyme.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.