ArticleDiabetes2008
Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 124 citations in OpenAlex.
- MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.The Journal of clinical investigation · 2015Trial
- Zeaxanthin Modulates Early Metabolic and Inflammatory Responses in db/db Mice: Associations with Intestinal Lipid Handling and Gut Microbiome Remodeling.Biomolecules · 2026Article
- Hepatic HuR modulates glucose metabolism through the C/EBPβ/PCK1 pathway.Molecular metabolism · 2026Article
- Mitochondrial control of glycerolipid synthesis by a PEP shuttle.bioRxiv : the preprint server for biology · 2026Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Therapeutic Potential of Myricitrin in aMolecules (Basel, Switzerland) · 2025Article
- Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.Biogerontology · 2025Review
- The Effects of Acute Temperature Changes on Transcriptomic Responses in the Liver of Leopard Coral Groupers (Antioxidants (Basel, Switzerland) · 2025Article
- Schisandrin B alleviates metabolic associated fatty liver disease by regulating the PPARγ signaling pathway and gut microbiota in mice.Frontiers in pharmacology · 2025Article
- Small molecules targeting selective PCK1 and PGC-1α lysine acetylation cause anti-diabetic action through increased lactate oxidation.Cell chemical biology · 2024Article
- Expression and functional significance of phosphoenolpyruvate carboxykinase 1 in uveal melanoma.Cell death discovery · 2024Article
- Article
- Hepatic ZBTB22 promotes hyperglycemia and insulin resistance via PEPCK1-driven gluconeogenesis.EMBO reports · 2023Article
- TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN.Cellular and molecular life sciences : CMLS · 2023Article
- Article
- Inhibition of Gluconeogenesis by Boldine in the Perfused Liver: Therapeutical Implication for Glycemic Control.International journal of hepatology · 2023Article
- Excessive gluconeogenesis causes the hepatic insulin resistance paradox and its sequelae.Heliyon · 2022Review
- Article
- The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.Science advances · 2022Article
- Combination of TRP channel dietary agonists induces energy expending and glucose utilizing phenotype in HFD-fed mice.International journal of obesity (2005) · 2022Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; encoded by Pck1) catalyzes the first committed step in gluconeogenesis. Extensive evidence demonstrates a direct correlation between PEPCK-C activity and glycemia control. Therefore, we aimed to evaluate the metabolic impact and their underlying mechanisms of knocking down hepatic PEPCK-C in a type 2 diabetic model. RESEARCH DESIGN AND
methodsPEPCK-C gene targeting was achieved using adenovirus-transduced RNAi. The study assessed several clinical symptoms of diabetes and insulin signaling in peripheral tissues, in addition to changes in gene expression, protein, and metabolites in the liver. Liver bioenergetics was also evaluated.
resultsTreatment resulted in reduced PEPCK-C mRNA and protein. After treatment, improved glycemia and insulinemia, lower triglyceride, and higher total and HDL cholesterol were measured. Unsterified fatty acid accumulation was observed in the liver, in the absence of de novo lipogenesis. Despite hepatic lipidosis, treatment resulted in improved insulin signaling in the liver, muscle, and adipose tissue. O(2) consumption measurements in isolated hepatocytes demonstrated unaltered mitochondrial function and a consequent increased cellular energy charge. Key regulatory factors (FOXO1, hepatocyte nuclear factor-4alpha, and peroxisome proliferator-activated receptor-gamma coactivator [PGC]-1alpha) and enzymes (G6Pase) implicated in gluconeogenesis were downregulated after treatment. Finally, the levels of Sirt1, a redox-state sensor that modulates gluconeogenesis through PGC-1alpha, were diminished.
conclusionsOur observations indicate that silencing PEPCK-C has direct impact on glycemia control and energy metabolism and provides new insights into the potential significance of the enzyme as a therapeutic target for the treatment 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.