ArticleJournal of hepatology2013
PEPCK-M expression in mouse liver potentiates, not replaces, PEPCK-C mediated gluconeogenesis.
Article in Journal of hepatology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- SLC25A35 carrier endows mitochondrial phosphoenolpyruvate with glyceroneogenesis.Life metabolism · 2026Article
- Depot-Specific White Adipose Tissue Remodeling Supports Non-Thermogenic Metabolic Homeostasis During Shallow Hibernation in Raccoon Dogs.International journal of molecular sciences · 2026Article
- Hepatic Gluconeogenesis and the Antidepressant Effects of Exercise: A Narrative Review.Metabolites · 2026Review
- The PCK2-Traf6-Tollip Axis Restricts PEDV Replication by Orchestrating Selective Autophagic Degradation of the Viral Nucleocapsid Protein.Transboundary and emerging diseases · 2026Article
- Feeding of high-quality hay modulates hepatic lipid and energy metabolism in weaned dairy calves.JDS communications · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Cytosolic PEPCK deficiency caused by a novel homozygous frame-shift variant presenting as resolved hypoglycemia and acute liver failure at birth.Molecular genetics and metabolism reports · 2025Article
- Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism.Cell reports · 2025Article
- Mitochondrial heterogeneity and adaptations to cellular needs.Nature cell biology · 2024Review
- Integrated Transcriptomic and Metabolomic Analyses Reveal Low-Temperature Tolerance Mechanism in Giant Freshwater PrawnAnimals : an open access journal from MDPI · 2023Article
- Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.Nature communications · 2023Article
- Article
- The SLC25A47 locus controls gluconeogenesis and energy expenditure.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Interactions between innate immunity and insulin signaling affect resistance to infection in insects.Frontiers in immunology · 2023Review
- Mitochondrial phosphoenolpyruvate carboxykinase promotes tumor growth in estrogen receptor-positive breast cancer via regulation of the mTOR pathway.Cancer medicine · 2023Article
- Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency.International journal of oral science · 2022Article
- Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells.Cell death & disease · 2022Article
- Article
- Simulation of the crosstalk between glucose and acetaminophen metabolism in a liver zonation model.Frontiers in pharmacology · 2022Article
- Ameliorative Effect of Oxytocin onFrontiers in public health · 2022Article
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9 authors.
Funding
Abstract
BACKGROUND &
aimsHepatic gluconeogenesis helps maintain systemic energy homeostasis by compensating for discontinuities in nutrient supply. Liver-specific deletion of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) abolishes gluconeogenesis from mitochondrial substrates, deregulates lipid metabolism and affects TCA cycle. While the mouse liver almost exclusively expresses PEPCK-C, humans equally present a mitochondrial isozyme (PEPCK-M). Despite clear relevance to human physiology, the role of PEPCK-M and its gluconeogenic potential remain unknown. Here, we test the significance of PEPCK-M in gluconeogenesis and TCA cycle function in liver-specific PEPCK-C knockout and WT mice.
methodsThe effects of the overexpression of PEPCK-M were examined by a combination of tracer studies and molecular biology techniques. Partial PEPCK-C re-expression was used as a positive control. Metabolic fluxes were evaluated in isolated livers by NMR using (2)H and (13)C tracers. Gluconeogenic potential, together with metabolic profiling, was investigated in vivo and in primary hepatocytes.
resultsPEPCK-M expression partially rescued defects in lipid metabolism, gluconeogenesis and TCA cycle function impaired by PEPCK-C deletion, while ∼10% re-expression of PEPCK-C normalized most parameters. When PEPCK-M was expressed in the presence of PEPCK-C, the mitochondrial isozyme amplified total gluconeogenic capacity, suggesting autonomous regulation of oxaloacetate to phosphoenolpyruvate fluxes by the individual isoforms.
conclusionsWe conclude that PEPCK-M has gluconeogenic potential per se, and cooperates with PEPCK-C to adjust gluconeogenic/TCA flux to changes in substrate or energy availability, hinting at a role in the regulation of glucose and lipid metabolism in the human liver.
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