ReviewJournal of diabetes investigation2021
Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases.
Review in Journal of diabetes investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Hepatocyte Growth Hormone Receptor Ablation Is Associated With Aging Phenotypes and Hepatic Mitochondrial Dysfunction.Aging cell · 2026Article
- Ginsenoside Rg2 Targeting PDHE1 α to Improve High Glucose-Induced Hippocampal Neuronal Damage Based on CETSA Experiment.Chinese journal of integrative medicine · 2026Article
- Pharmacological Inhibition of Pyruvate Dehydrogenase Kinase 4 Enhances Insulin Sensitivity in Mouse Models of Diabetes and Obesity.Journal of obesity & metabolic syndrome · 2026Article
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- PDK4 Regulates Inflammatory Injury in Acute-on-chronic Liver Failure by Phosphorylating STAT1-mediated M1 Polarization of Macrophages.Journal of clinical and translational hepatology · 2025Article
- Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.JCI insight · 2025Article
- Review
- Reciprocal rescue of Wolfram syndrome by two causative genes.EMBO reports · 2025Article
- Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.Journal of physiology and biochemistry · 2025Review
- Distinct Impact of Doxorubicin on Skeletal Muscle and Fat Metabolism in Mice: Without Dexrazoxane Effect.International journal of molecular sciences · 2025Article
- Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.iScience · 2024Review
- Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.The Journal of clinical investigation · 2024Article
- Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Genetic Ablation of Pyruvate Dehydrogenase Kinase Isoform 4 Gene Enhances Recovery from Hyperoxic Lung Injury: Insights into Antioxidant and Inflammatory Mechanisms.Biomedicines · 2024Article
- Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip.Nature communications · 2024Article
- Systemic proteome phenotypes reveal defective metabolic flexibility in Mecp2 mutants.Human molecular genetics · 2023Article
- Inflammation primes the kidney for recovery by activating AZIN1 A-to-I editing.bioRxiv : the preprint server for biology · 2023Article
- Exploring diet-induced promoter hypomethylation and PDK4 overexpression: implications for type 2 diabetes mellitus.Molecular biology reports · 2023Article
- Systemic Proteome Phenotypes Reveal Defective Metabolic Flexibility in Mecp2 Mutants.bioRxiv : the preprint server for biology · 2023Article
- O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function.Communications biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Good health depends on the maintenance of metabolic flexibility, which in turn is dependent on the maintenance of regulatory flexibility of a large number of regulatory enzymes, but especially the pyruvate dehydrogenase complex (PDC), because of its central role in carbohydrate metabolism. Flexibility in regulation of PDC is dependent on rapid changes in the phosphorylation state of PDC determined by the relative activities of the pyruvate dehydrogenase kinases (PDKs) and the pyruvate dehydrogenase phosphatases. Inactivation of the PDC by overexpression of PDK4 contributes to hyperglycemia, and therefore the serious health problems associated with diabetes. Loss of regulatory flexibility of PDC occurs in other disease states and pathological conditions that have received less attention than diabetes. These include cancers, non-alcoholic fatty liver disease, cancer-induced cachexia, diabetes-induced nephropathy, sepsis and amyotrophic lateral sclerosis. Overexpression of PDK4, and in some situations, the other PDKs, as well as under expression of the pyruvate dehydrogenase phosphatases, leads to inactivation of the PDC, mitochondrial dysfunction and deleterious effects with health consequences. The possible basis for this phenomenon, along with evidence that overexpression of PDK4 results in phosphorylation of "off-target" proteins and promotes excessive transport of Ca
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