ArticleScientific reports2015
Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Mechanisms and Predisposing Conditions for Statin-Induced New-Onset Type 2 Diabetes Mellitus: A Paradox Relative to Their Pleiotropic Metabolic Effects.Endocrinology, diabetes & metabolism · 2026Review
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- Short-Term Statin Therapy Induces Hepatic Insulin Resistance Through HNF4α/PAQR9/PPM1α Axis Regulated AKT Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- Review
- Atypical functions of xenobiotic receptors in lipid and glucose metabolism.Medical review (2021) · 2022Review
- Developmental programming: Impact of prenatal bisphenol-A exposure on liver and muscle transcriptome of female sheep.Toxicology and applied pharmacology · 2022Article
- Label-free chemical imaging of cytochrome P450 activity by Raman microscopy.Communications biology · 2022Article
- PXR activation impairs hepatic glucose metabolism partlyActa pharmaceutica Sinica. B · 2022Article
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Updated Understanding of the Crosstalk Between Glucose/Insulin and Cholesterol Metabolism.Frontiers in cardiovascular medicine · 2022Review
- Review
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review.International journal of molecular sciences · 2021Review
- Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease.Molecular metabolism · 2021Review
- The xenobiotic receptors PXR and CAR in liver physiology, an update.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Review
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Statin therapy is known to increase blood glucose levels in humans. Statins utilize pregnane X receptor (PXR) and serum/glucocorticoid regulated kinase 2 (SGK2) to activate phosphoenolpyruvate carboxykinase 1 (PEPCK1) and glucose-6-phosphatase (G6Pase) genes, thereby increasing glucose production in human liver cells. Here, the novel statin/PXR/SGK2-mediated signaling pathway has now been characterized for hepatic gluconeogenesis. Statin-activated PXR scaffolds the protein phosphatase 2C (PP2C) and SGK2 to stimulate PP2C to dephosphorylate SGK2 at threonine 193. Non-phosphorylated SGK2 co-activates PXR-mediated trans-activation of promoters of gluconeogenic genes in human liver cells, thereby enhancing gluconeogenesis. This gluconeogenic statin-PXR-SGK2 signal is not present in mice, in which statin treatment suppresses hepatic gluconeogenesis. These findings provide the basis for statin-associated side effects such as an increased risk for Type 2 diabetes.
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Registered trials
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.