ArticleThe Journal of pharmacology and experimental therapeutics2014
Serum- and glucocorticoid-regulated kinase 2 determines drug-activated pregnane X receptor to induce gluconeogenesis in human liver cells.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- 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
- B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity.Nature communications · 2024Article
- PXR activation impairs hepatic glucose metabolism partlyActa pharmaceutica Sinica. B · 2022Article
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Review
- Serum- and glucocorticoid-induced kinase drives hepatic insulin resistance by directly inhibiting AMP-activated protein kinase.Cell reports · 2021Article
- Review
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
- Article
- Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo.The Journal of endocrinology · 2020Article
- Natural substance rutin versus standard drug atorvastatin in a treatment of metabolic syndrome-like condition.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Article
- The Roles of Xenobiotic Receptors: Beyond Chemical Disposition.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk.Expert opinion on drug metabolism & toxicology · 2016Review
- Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions.Frontiers in pharmacology · 2016Review
- Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Drug activation of the human nuclear pregnane X receptor (PXR) induced gluconeogenic genes and increased glucose production. In this study, we have determined that serum- and glucocorticoid-regulated kinase 2 (SGK2) is an essential factor that mediates this PXR-regulated glucose 6-phosphatase (G6Pase) induction and glucose production. Both SGK2 and G6Pase mRNAs were increased in rifampicin-treated HepG2 cells stably expressing human PXR. Reporter and chromatin immunoprecipitation assays delineated PXR activation of the SGK2 gene to a distal and proximal DNA sequence within its promoter: distal PXR response element (-2587/-2209) and proximal PXR response element (-115/-75), respectively. Small interfering RNA (siRNA) knockdown of SGK2 severely attenuated PXR-regulated induction of G6Pase as well as glucose production. SGK2 constitutes an insulin-independent signal pathway to regulate gluconeogenesis because siRNA knockdown of the insulin-responsive transcription factor forkhead box protein O1 did not affect rifampicin induction of G6Pase. Rifampicin treatment of two different samples of human primary hepatocytes revealed that PXR induces G6Pase in the presence of high levels of SGK2, whereas PXR represses G6Pase in its absence. Mediating PXR activation of the G6Pase gene is the first biological role found for hepatic SGK2 and might have therapeutic implications for side effects, such as diabetes, caused by drugs that activate PXR.
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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.