Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.

ABSTRACT: Metformin is currently the most widely used drug for the treatment of type 2 diabetes. Mechanistically, metformin interacts with many protein kinases and transcription factors that alter the expression of numerous downstream target genes governing lipid metabolism, cell proliferation, and drug metabolism. The constitutive androstane receptor (CAR, NR1i3), a known xenobiotic sensor, has recently been recognized as a novel signaling molecule, in that its activation could be regulated by protein kinases in addition to the traditional ligand binding. We show that metformin could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the phosphorylation status of CAR. In human hepatocytes, metformin robustly suppressed the expression of CYP2B6 induced by both in

SUBMITTER: Yang H 

PROVIDER: S-EPMC3913356 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature