FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2034217761> ?p ?o ?g. }

• W2034217761 endingPage "1780" @default.
• W2034217761 startingPage "1771" @default.
• W2034217761 abstract "Metformin is widely used in the treatment of type-2 diabetes. The pleotropic effects of metformin on glucose and lipid metabolism have been proposed to be mediated by the activation of AMP-activated protein kinase (AMPK) and the subsequent up-regulation of small heterodimer partner (SHP). SHP suppresses the functions of several nuclear receptors involved in the regulation of hepatic metabolism, including pregnane X receptor (PXR), which is referred to as a master regulator of drug/xenobiotic metabolism. In this study, we hypothesize that metformin suppresses the expression of CYP3A4, a main detoxification enzyme and a target gene of PXR, due to SHP up-regulation. We employed various gene reporter assays in cell lines and qRT-PCR in human hepatocytes and in Pxr(-/-) mice. We show that metformin dramatically suppresses PXR-mediated expression of CYP3A4 in hepatocytes. Consistently, metformin significantly suppressed the up-regulation of Cyp3a11 mRNA in the liver and intestine of wild-type mice, but not in Pxr(-/-) mice. A mechanistic investigation of the phenomenon showed that metformin does not significantly up-regulate SHP in human hepatocytes. We further demonstrate that AMPK activation is not involved in this process. We show that metformin disrupts PXR's interaction with steroid receptor coactivator-1 (SRC1) in a two-hybrid assay independently of the PXR ligand binding pocket. Metformin also inhibited vitamin D receptor-, glucocorticoid receptor- and constitutive androstane receptor (CAR)-mediated induction of CYP3A4 mRNA in human hepatocytes. We show, therefore, a suppressive effect of metformin on PXR and other ligand-activated nuclear receptors in transactivation of the main detoxification enzyme CYP3A4 in human hepatocytes." @default.
• W2034217761 created "2016-06-24" @default.
• W2034217761 creator A5020824245 @default.
• W2034217761 creator A5021082677 @default.
• W2034217761 creator A5023930723 @default.
• W2034217761 creator A5042484633 @default.
• W2034217761 creator A5054253771 @default.
• W2034217761 creator A5064487640 @default.
• W2034217761 creator A5073947500 @default.
• W2034217761 date "2011-12-01" @default.
• W2034217761 modified "2023-10-01" @default.
• W2034217761 title "Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene" @default.
• W2034217761 cites W1496168405 @default.
• W2034217761 cites W1967575685 @default.
• W2034217761 cites W1967904535 @default.
• W2034217761 cites W1970205234 @default.
• W2034217761 cites W1977027014 @default.
• W2034217761 cites W1978943768 @default.
• W2034217761 cites W1979217402 @default.
• W2034217761 cites W1991633055 @default.
• W2034217761 cites W1994405711 @default.
• W2034217761 cites W1995069275 @default.
• W2034217761 cites W1997003352 @default.
• W2034217761 cites W1998622278 @default.
• W2034217761 cites W2003599782 @default.
• W2034217761 cites W2004032561 @default.
• W2034217761 cites W2006502890 @default.
• W2034217761 cites W2008785161 @default.
• W2034217761 cites W2012104309 @default.
• W2034217761 cites W2017784962 @default.
• W2034217761 cites W2019354525 @default.
• W2034217761 cites W2039079930 @default.
• W2034217761 cites W2039212784 @default.
• W2034217761 cites W2041290320 @default.
• W2034217761 cites W2044095562 @default.
• W2034217761 cites W2045938951 @default.
• W2034217761 cites W2049604806 @default.
• W2034217761 cites W2051092460 @default.
• W2034217761 cites W2055911345 @default.
• W2034217761 cites W2060600856 @default.
• W2034217761 cites W2070428103 @default.
• W2034217761 cites W2080680563 @default.
• W2034217761 cites W2087279229 @default.
• W2034217761 cites W2095860665 @default.
• W2034217761 cites W2123081876 @default.
• W2034217761 cites W2125306830 @default.
• W2034217761 cites W2136560821 @default.
• W2034217761 cites W2138226825 @default.
• W2034217761 cites W2138319716 @default.
• W2034217761 cites W2144280397 @default.
• W2034217761 cites W2145540652 @default.
• W2034217761 cites W2148672071 @default.
• W2034217761 cites W2151282765 @default.
• W2034217761 cites W2154015838 @default.
• W2034217761 cites W2155744138 @default.
• W2034217761 cites W2156715171 @default.
• W2034217761 cites W2164475967 @default.
• W2034217761 cites W2176815171 @default.
• W2034217761 cites W2315903617 @default.
• W2034217761 doi "https://doi.org/10.1016/j.bcp.2011.08.023" @default.
• W2034217761 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3205227" @default.
• W2034217761 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21920351" @default.
• W2034217761 hasPublicationYear "2011" @default.
• W2034217761 type Work @default.
• W2034217761 sameAs 2034217761 @default.
• W2034217761 citedByCount "70" @default.
• W2034217761 countsByYear W20342177612012 @default.
• W2034217761 countsByYear W20342177612013 @default.
• W2034217761 countsByYear W20342177612014 @default.
• W2034217761 countsByYear W20342177612015 @default.
• W2034217761 countsByYear W20342177612016 @default.
• W2034217761 countsByYear W20342177612017 @default.
• W2034217761 countsByYear W20342177612018 @default.
• W2034217761 countsByYear W20342177612019 @default.
• W2034217761 countsByYear W20342177612020 @default.
• W2034217761 countsByYear W20342177612021 @default.
• W2034217761 countsByYear W20342177612022 @default.
• W2034217761 countsByYear W20342177612023 @default.
• W2034217761 crossrefType "journal-article" @default.
• W2034217761 hasAuthorship W2034217761A5020824245 @default.
• W2034217761 hasAuthorship W2034217761A5021082677 @default.
• W2034217761 hasAuthorship W2034217761A5023930723 @default.
• W2034217761 hasAuthorship W2034217761A5042484633 @default.
• W2034217761 hasAuthorship W2034217761A5054253771 @default.
• W2034217761 hasAuthorship W2034217761A5064487640 @default.
• W2034217761 hasAuthorship W2034217761A5073947500 @default.
• W2034217761 hasBestOaLocation W20342177612 @default.
• W2034217761 hasConcept C104317684 @default.
• W2034217761 hasConcept C109650736 @default.
• W2034217761 hasConcept C126322002 @default.
• W2034217761 hasConcept C1292079 @default.
• W2034217761 hasConcept C132040763 @default.
• W2034217761 hasConcept C134018914 @default.
• W2034217761 hasConcept C150194340 @default.
• W2034217761 hasConcept C170493617 @default.
• W2034217761 hasConcept C179639408 @default.
• W2034217761 hasConcept C183481951 @default.
• W2034217761 hasConcept C184235292 @default.

• next