Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway.

Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e.