Lymphocyte cytochrome P450-CYP2E1 expression in human IDDM subjects.

ABSTRACT

Cytochrome P4502E1, a phase I enzyme, has been shown to be induced in liver samples from diabetic and obese rats. One study demonstrated elevated levels of CYP2E1 in children with IDDM, using Western blot analysis. The aim of this investigation was to determine CYP2E1 expression in peripheral blood lymphocytes from eight well-controlled IDDM and eight sex- and age-matched control subjects using Western blot analysis and Phoretix image analysis. Levels of CYP2E1 were low to undetectable in human lymphocytes from healthy control subjects. However, levels of CYP2E1 were elevated in lymphocytes from IDDM subjects (mean 3.1-fold higher). The elevated levels of CYP2E1 in the IDDM subjects showed no correlation with HbA(1c) nor duration of IDDM; however, there were marked inter-individual differences in levels of induction of CYP2E1 between all subjects. The results of this study suggest that in human IDDM subjects, even with good metabolic control, expression of CYP2E1 is elevated when compared to controls. CYP2E1 is known to generate ROS in vivo, the modulation of this isoform in lymphocytes from IDDM subjects, could well add to the oxidative stress associated with IDDM and the development of associated complications.