Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus.

ABSTRACT:

Background and purpose

Patients with diabetes mellitus require pharmacotherapy with numerous medications. However, the effect of diabetes on drug biotransformation is not well understood. Our goal was to investigate the effect of diabetes on liver cytochrome P450 3As, the most abundant phase I drug-metabolizing enzymes in humans.

Experimental approach

Human liver microsomal fractions (HLMs) were prepared from diabetic (n= 12) and demographically matched nondiabetic (n= 12) donors, genotyped for CYP3A4*1B and CYP3A5*3 polymorphisms. Cytochrome P450 3A4, 3A5 and 2E1 mRNA expression, protein level and enzymatic activity were compared between the two groups.

Key results

Midazolam 1'- or 4-hydroxylation and testosterone 6β-hydroxylation, catalyzed by P450 3A, were markedly

SUBMITTER: Dostalek M 

PROVIDER: S-EPMC3130941 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature