Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F11%3A33118888" target="_blank" >RIV/61989592:15310/11:33118888 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11160/11:10100402
Result on the web
<a href="http://dx.doi.org/10.1016/j.bcp.2011.08.023" target="_blank" >http://dx.doi.org/10.1016/j.bcp.2011.08.023</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2011.08.023" target="_blank" >10.1016/j.bcp.2011.08.023</a>
Alternative languages
Result language
angličtina
Original language name
Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene
Original language description
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-regulationof 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 hepatocytesand 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-t
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FR - Pharmacology and apothecary chemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Pharmacology
ISSN
0006-2952
e-ISSN
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Volume of the periodical
82
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
1771-1780
UT code for WoS article
000296931400026
EID of the result in the Scopus database
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