ArticleThe Biochemical journal2006
Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis during starvation.
Article in The Biochemical journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 140 citations in OpenAlex.
- Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans.Science advances · 2018Trial
- Regulation of PDH via cysteine oxidation on DLAT.Nature communications · 2026Article
- Exercise Metabolic Memory Halts Pathological Cardiac Hypertrophy via PDK4.Circulation research · 2026Article
- Marked Increases in Continuous Glucose Monitor-Detected Hypoglycemia During a Seven-Day Water-Only Fast in Healthy Men and Women.Journal of diabetes science and technology · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- PFKFB2 Is Pivotal for Metabolic Flexibility and Differential Glucose Utilization.Journal of the American Heart Association · 2025Article
- Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Effects of seven days' fasting on physical performance and metabolic adaptation during exercise in humans.Nature communications · 2025Article
- PDK4-mediated metabolic reprogramming is a potential therapeutic target for neovascular age-related macular degeneration.Cell death & disease · 2024Article
- Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice.Diabetes & metabolism journal · 2024Article
- Identification and analysis of mitochondria-related central genes in steroid-induced osteonecrosis of the femoral head, along with drug prediction.Frontiers in endocrinology · 2024Article
- Molecular and Metabolic Analysis of Arsenic-Exposed Humanized AS3MT Mice.Environmental health perspectives · 2023Article
- Functional and molecular profiling of fasted piglets reveals decreased energy metabolic function and cell proliferation in the small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Article
- The Role of Pyruvate Metabolism in Mitochondrial Quality Control and Inflammation.Molecules and cells · 2023Review
- Inhibition of Pyruvate Dehydrogenase in the Heart as an Initiating Event in the Development of Diabetic Cardiomyopathy.Antioxidants (Basel, Switzerland) · 2023Review
- Nitric oxide regulation of cellular metabolism: Adaptive tuning of cellular energy.Nitric oxide : biology and chemistry · 2023Review
- Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice.Frontiers in endocrinology · 2023Article
- Sepsis, pyruvate, and mitochondria energy supply chain shortage.Journal of leukocyte biology · 2022Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation during starvation to conserve substrates for gluconeogenesis. The role of PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this mechanism was investigated with PDHK4-/- mice (homozygous PDHK4 knockout mice). Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type mice. The activity state of PDC (percentage dephosphorylated and active) is greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver of starved PDHK4-/- mice. Intermediates of the gluconeogenic pathway are lower in concentration in the liver of starved PDHK4-/- mice, consistent with a lower rate of gluconeogenesis due to a substrate supply limitation. The concentration of gluconeogenic substrates is lower in the blood of starved PDHK4-/- mice, consistent with reduced formation in peripheral tissues. Isolated diaphragms from starved PDHK4-/- mice accumulate less lactate and pyruvate because of a faster rate of pyruvate oxidation and a reduced rate of glycolysis. BCAAs (branched chain amino acids) are higher in the blood in starved PDHK4-/- mice, consistent with lower blood alanine levels and the importance of BCAAs as a source of amino groups for alanine formation. Non-esterified fatty acids are also elevated more in the blood of starved PDHK4-/- mice, consistent with lower rates of fatty acid oxidation due to increased rates of glucose and pyruvate oxidation due to greater PDC activity. Up-regulation of PDHK4 in tissues other than the liver is clearly important during starvation for regulation of PDC activity and glucose homoeostasis.
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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.