Abstract
We have previously shown that P450 dependent hepatic metabolism is increased in poorly controlled insulin dependent diabetes mellitus (IDDM) affecting all three isozymes involved in antipyrine metabolism (Ped. Res. 21:346A, 1987). We now describe elevated P50j in lymphocytes of poorly controlled IDDM patients. P450j plays a major role in the metabolism of nitrosamine, a carcinogen, and in metabolic conversion of acetoacetate and acetone to acetol. Levels of P450j are increased in diabetic animals by specific mRNA stablization (Molec. Endocr. 1:542, 1987). In this study, P450j was measured in peripheral lymphocytes (5ml of blood), of 8 patients with IDDM (age 6-14, mean 10.2 yr) in poor control. Their Hgb A1 was 13.2±2.1% (nl<7.8%). P450 was measured using a polyclonal antibody (AB) against P450j. Lymphocytes were obtained from nl volunteers and IDDM patients, grown in tissue culture at 37°C for 4 days, in the presence of mitogen. Lymphocytes were homogenized and analyzed by SDS polyacrylamide gel electrophoresis followed by Western blot analysis using polyclonal AB's against P450j. Levels of P450j in IDDM patients were 3-6 times higher than those of nl controls. The highest P450j levels (5 and 6 fold increases) were seen in the 2 patients with the highest Hgb A1 levels (12, 14.3%). This is the first direct demonstration of a potentially reversible elevation of a member of the cytochrome P450 gene family in IDDM using a readily available tissue source.
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Saenger, P., Veech, R., Song, B. et al. 12 INCREASED CYTOCHROME P-450 (P450j) LEVELS IN LYMPHOCYTES OF CHILDREN WITH POORLY CONTROLLED INSULIN DEPENDENT DIABETES MELLITUS (IDDM). Pediatr Res 24, 519 (1988). https://doi.org/10.1203/00006450-198810000-00033
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DOI: https://doi.org/10.1203/00006450-198810000-00033