Alteration of cytochrome P450s activity under diabetic conditions and its impact on the development of diabetes mellitus

Cytochrome P450s(CYP450s)is one of the most important phase-I drug-metabolizing enzyme family that participates in the metabolism of most clinical drugs in liver and intestine. Accumulative evidences have reported that the activities and expressions of hepatic CYP450s exhibited significant alterations under diabetic condition. This article summarizes the induction or inhibition of different isoforms of CYP450s, including CYP3A, CYP2E1 and CYP1A2, in clinical or experimental diabetic conditions, and analyzes the impact of species difference, types and progression of diabetes on CYP450s activity. The article further lists the altered pharmacokinetic behaviors as well as adverse drug effects due to alteration of CYP450s in reported diabetic cases. The correlations between the altered metabolism of endocrines, the aggravation of insulin resistance, and the alteration of CYP450s activity are illustrated to shed more light on the pathogenesis of diabetes.