ArticleMolecular and cellular endocrinology2010
Regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) gene expression by glucocorticoids and insulin.
Article in Molecular and cellular endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 141 citations in OpenAlex.
- Renal single-nucleus transcriptomic of a new model of cardiovascular-kidney-metabolic syndrome in aging swine.American journal of physiology. Renal physiology · 2026Article
- Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 alleviates Alzheimer's disease by reducing neuronal insulin resistance and restoring energy homeostasis.Neural regeneration research · 2026Article
- Review
- Liver transcriptome dynamics in Holstein cows during the periparturient transition.Scientific reports · 2026Article
- Dietary salt impairs circadian physiological metabolic adaptations in salt-sensitive hypertension.Function (Oxford, England) · 2026Article
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability.Journal of neurochemistry · 2026Review
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Review
- Methodologies to Identify Metabolic Pathway Differences Between Emaciated and Moderately Conditioned Horses: A Review of Multiple Gene Expression Techniques.Animals : an open access journal from MDPI · 2025Review
- Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK-PDC axis.Reproductive biology and endocrinology : RB&E · 2025Article
- Thermoneutral housing has limited effects on social isolation-induced bone loss in male C57BL/6J mice.JBMR plus · 2025Article
- Reducing PDK4 level constitutes a pivotal mechanism for glucocorticoids to impede osteoblastic differentiation through the enhancement of ferroptosis in mesenchymal stem cells.Stem cell research & therapy · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.Journal of physiology and biochemistry · 2025Review
- Development of novel liver-targeting glucocorticoid prodrugs.Medicine in drug discovery · 2024Article
- Elevated Norepinephrine Stimulates Adipocyte Hyperplasia in Ovine Fetuses With Placental Insufficiency and IUGR.Endocrinology · 2023Article
- Targeting PDK2 rescues stress-induced impaired brain energy metabolism.Molecular psychiatry · 2023Article
- The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4.Diabetes & metabolism journal · 2023Review
- Longitudinal Epigenome-Wide Analysis of Kidney Transplant Recipients Pretransplant and Posttransplant.Kidney international reports · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA. Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK) inhibits its activity. The expression of the pyruvate dehydrogenase kinase 4 (PDK4) gene is increased in fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. Transcription of the PDK4 gene is elevated by glucocorticoids and inhibited by insulin. In this study, we have investigated the factors involved in the regulation of the PDK4 gene by these hormones. Glucocorticoids stimulate PDK4 through two glucocorticoid receptor (GR) binding sites located more than 6000 base pairs upstream of the transcriptional start site. Insulin inhibits the glucocorticoid induction in part by causing dissociation of the GR from the promoter. Previously, we found that the estrogen related receptor alpha (ERRalpha) stimulates the expression of PDK4. Here, we determined that one of the ERRalpha binding sites contributes to the insulin inhibition of PDK4. A binding site for the forkhead transcription factor (FoxO1) is adjacent to the ERRalpha binding sites. FoxO1 participates in the glucocorticoid induction of PDK4 and the regulation of this gene by insulin. Our data demonstrate that glucocorticoids and insulin each modulate PDK4 gene expression through complex hormone response units that contain multiple factors.
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