ArticleBritish journal of pharmacology2013
The constitutive androstane receptor activator 4-[(4R,6R)-4,6-diphenyl-1,3-dioxan-2-yl]-N,N-dimethylaniline inhibits the gluconeogenic genes PEPCK and G6Pase through the suppression of HNF4α and FOXO1 transcriptional activity.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Mechanistic insights into CAR-mediated repression of the HNF4α-FABP1 axis and inhibition of HepG2 cell proliferation.Pharmacological research · 2026Article
- The Pivotal Role of GR-CAR Pathway in Fetal Programming of Hepatic Cytochrome P450 3A Alteration in Adulthood.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Degraded Polysaccharides fromFoods (Basel, Switzerland) · 2025Article
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Mechanistic insights into the role of FOXO in diabetic retinopathy.American journal of translational research · 2022Review
- Yes-Associated Protein Is Crucial for Constitutive Androstane Receptor-Driven Hepatocyte Proliferation But Not for Induction of Drug Metabolism Genes in Mice.Hepatology (Baltimore, Md.) · 2021Article
- Review
- Noncanonical Constitutive Androstane Receptor Signaling in Gene Regulation.International journal of molecular sciences · 2020Review
- TCPOBOP-Induced Hepatomegaly and Hepatocyte Proliferation are Attenuated by Combined Disruption of MET and EGFR Signaling.Hepatology (Baltimore, Md.) · 2019Article
- Dietary Bile Acids Enhance Growth, and Alleviate Hepatic Fibrosis Induced by a High Starch Diet via AKT/FOXO1 and cAMP/AMPK/SREBP1 Pathway inFrontiers in physiology · 2019Article
- Identification of Modulators That Activate the Constitutive Androstane Receptor From the Tox21 10K Compound Library.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Chlorogenic Acid Targeting of the AKT PH Domain Activates AKT/GSK3β/FOXO1 Signaling and Improves Glucose Metabolism.Nutrients · 2018Article
- Enteric Microbiota⁻Gut⁻Brain Axis from the Perspective of Nuclear Receptors.International journal of molecular sciences · 2018Review
- Teriflunomide Is an Indirect Human Constitutive Androstane Receptor (CAR) Activator Interacting With Epidermal Growth Factor (EGF) Signaling.Frontiers in pharmacology · 2018Article
- Modulation of glucose metabolism by a natural compound from Chloranthus japonicus via activation of AMP-activated protein kinase.Scientific reports · 2017Article
- Article
- Nonsterol Isoprenoids Activate Human Constitutive Androstane Receptor in an Isoform-Selective Manner in Primary Cultured Mouse Hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe dual role of the constitutive androstane receptor (CAR) as both a xenosensor and a regulator of endogenous energy metabolism (lipogenesis and gluconeogenesis) has recently gained acceptance. Here, we investigated the effects of 4-[(4R,6R)-4,6-diphenyl-1,3-dioxan-2-yl]-N,N-dimethylaniline (transpDMA), an effective CAR activator, on the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in rat livers. EXPERIMENTAL APPROACH: The effects of transpDMA were investigated in normal and high-fat diet-fed Wistar rats using real-time PCR, Western blotting, chromatin immunoprecipitation assays (ChIP), glucose tolerance test and insulin tolerance test. KEY
resultsThe expression of the gluconeogenic enzymes PEPCK and G6Pase was repressed by transpDMA treatment under fasting conditions. Long-term CAR activation by transpDMA significantly reduced fasting blood glucose levels and improved glucose homeostasis and insulin sensitivity in high-fat diet-fed rats. The metabolic benefits of CAR activation by transpDMA may have resulted from the inhibition of hepatic gluconeogenic genes. ChIP assays demonstrated that transpDMA prevented the binding of forkhead box O1 (FOXO1) to insulin response sequences in the PEPCK and G6Pase gene promoters in rat livers. Moreover, transpDMA-activated CAR inhibited hepatocyte nuclear factor-4α (HNF4α) transactivation by competing with HNF4α for binding to the specific binding element (DR1-site) in the gluconeogenic gene promoters. CONCLUSIONS AND IMPLICATIONS: Our results provide evidence to support the conclusion that transpDMA inhibits the gluconeogenic genes PEPCK and G6Pase through suppression of HNF4α and FOXO1 transcriptional activity.
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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.