Glucose-dependent regulation of pregnane X receptor is modulated by AMP-activated protein kinase.

ABSTRACT: Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxification and clearance of drugs and foreign compounds from the liver. There has been mounting evidence of crosstalk between the drug metabolism pathway and the energy metabolism pathway, but little is known about this cross-regulation. To further delineate the energy metabolism and drug metabolism crosstalk in this study, we exposed HepG2 cells to varying glucose concentrations. We observed that PXR activity was induced under high-glucose conditions. This finding is consistent with previous clinical reports of increased drug clearance in patients with untreated diabetes. We demonstrated that AMP-activated protein kinase (AMPK) modulates PXR transcriptional activity and that pharmacologically manipulated AMPK activa

SUBMITTER: Oladimeji PO 

PROVIDER: S-EPMC5402287 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature