ArticlePloS one2013
Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice.Nature metabolism · 2025Article
- Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.Journal of physiology and biochemistry · 2025Review
- Exploring Renal Pyruvate Metabolism as a Therapeutic Avenue for Diabetic Kidney Injury.Diabetes & metabolism journal · 2024Article
- Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing.bioRxiv : the preprint server for biology · 2023Article
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- Enhanced CaNature communications · 2023Article
- Metabolic Inflexibility as a Pathogenic Basis for Atrial Fibrillation.International journal of molecular sciences · 2022Review
- Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, ameliorates type 2 diabetes via reduced gluconeogenesis.Heliyon · 2022Article
- Dynamic Mitochondrial Proteome Under Polyamines Treatment in Cardiac Aging.Frontiers in cell and developmental biology · 2022Article
- Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4.Oxidative medicine and cellular longevity · 2022Article
- Expression dynamics of pregnane X receptor-controlled genes in 3D primary human hepatocyte spheroids.Archives of toxicology · 2022Article
- Hepatocyte-SpecificNutrients · 2021Article
- BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate.International journal of molecular sciences · 2021Article
- Suppression of Pyruvate Dehydrogenase Kinase by Dichloroacetate in Cancer and Skeletal Muscle Cells Is Isoform Specific and Partially Independent of HIF-1α.International journal of molecular sciences · 2021Article
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance.Physiological reports · 2021Article
- 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.Journal of diabetes investigation · 2021Review
- Dynamic Glucose Disposal is Driven by Reduced Endogenous Glucose Production in Response to Voluntary Wheel Running: A Stable Isotope Approach.American journal of physiology. Endocrinology and metabolism · 2020Article
- PDK4-Deficiency Reprograms Intrahepatic Glucose and Lipid Metabolism to Facilitate Liver Regeneration in Mice.Hepatology communications · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Pyruvate dehydrogenase kinases (PDK1-4) play a critical role in the inhibition of the mitochondrial pyruvate dehydrogenase complex especially when blood glucose levels are low and pyruvate can be conserved for gluconeogenesis. Under diabetic conditions, the Pdk genes, particularly Pdk4, are often induced, and the elevation of the Pdk4 gene expression has been implicated in the increased gluconeogenesis in the liver and the decreased glucose utilization in the peripheral tissues. However, there is no direct evidence yet to show to what extent that the dysregulation of hepatic Pdk genes attributes to hyperglycemia and insulin resistance in vivo. To address this question, we crossed Pdk2 or Pdk4 null mice with a diabetic model that is deficient in hepatic insulin receptor substrates 1 and 2 (Irs1/2). Metabolic analyses reveal that deletion of the Pdk4 gene had better improvement in hyperglycemia and glucose tolerance than knockout of the Pdk2 gene whereas the Pdk2 gene deletion showed better insulin tolerance as compared to the Pdk4 gene inactivation on the Irs1/2 knockout genetic background. To examine the specific hepatic effects of Pdks on diabetes, we also knocked down the Pdk2 or Pdk4 gene using specific shRNAs. The data also indicate that the Pdk4 gene knockdown led to better glucose tolerance than the Pdk2 gene knockdown. In conclusion, our data suggest that hepatic Pdk4 may be critically involved in the pathogenesis of diabetes.
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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.