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Lymphocyte cytochrome P450-CYP2E1 expression in human IDDM subjects
M P Hannon-Fletcher1, M J O'Kane, K W Moles
1Cancer and Ageing Research Group, University of Ulster, Cromore Road, Coleraine, County Londonderry BT52 1SA, UK. mp.hannon@ulst.ac.uk
Summary
Levels of Cytochrome P450 2E1 (CYP2E1) were significantly elevated in the lymphocytes of individuals with insulin-dependent diabetes mellitus (IDDM). This increased CYP2E1 expression may contribute to oxidative stress in IDDM patients.
Area of Science:
- Biochemistry
- Immunology
- Metabolic Disorders
Background:
- Cytochrome P450 2E1 (CYP2E1) is a phase I enzyme implicated in various metabolic processes.
- Previous studies indicated CYP2E1 induction in diabetic and obese animal models, and elevated levels in children with IDDM.
- Oxidative stress is a known factor in the development of diabetic complications.
Purpose of the Study:
- To investigate CYP2E1 expression in peripheral blood lymphocytes of well-controlled IDDM subjects compared to healthy controls.
- To assess the relationship between CYP2E1 levels, glycemic control (HbA1c), and duration of IDDM.
Main Methods:
- Western blot analysis was employed to quantify CYP2E1 levels.
- Phoretix image analysis was used for quantitative assessment of protein expression.
- Peripheral blood lymphocytes were isolated from eight IDDM patients and eight age- and sex-matched controls.
Main Results:
- CYP2E1 levels were low to undetectable in lymphocytes from healthy control subjects.
- A significant elevation (mean 3.1-fold) of CYP2E1 was observed in lymphocytes from IDDM subjects.
- No correlation was found between elevated CYP2E1 levels and HbA1c or duration of IDDM, but inter-individual variations were noted.
Conclusions:
- CYP2E1 expression is upregulated in lymphocytes of IDDM patients, even with good metabolic control.
- Elevated CYP2E1 in IDDM lymphocytes may exacerbate oxidative stress, potentially contributing to disease complications.
- Further research is warranted to explore the role of CYP2E1 modulation in IDDM pathogenesis.

