Alterations in the gene expression of drug and arachidonic acid-metabolizing Cyp450 in the livers of controlled and uncontrolled insulin-dependent diabetic mice.

BACKGROUND

Diabetic patients have lower capacity to metabolize drugs in comparison to normal people. Therefore, the present study aimed to investigate the alterations in gene expression of drug and arachidonic acid metabolizing cytochrome p450s (cyp450s) in the livers of controlled (CDM) and uncontrolled (UDM) insulin-dependent diabetic mice.

METHODS

Balb/c mice were treated with single dose of streptozocin (240 mg/kg) to induce diabetes and compared with control group, which was treated with citric buffer (pH =4.5). After 3 days, the blood glucose level was measured to confirm the induction of diabetes. Normalization of blood glucose level in diabetic mice was achieved after 0.1 mL/kg Mixtard® insulin therapy for more 5 days. Then, the mice livers were isolated to extract RNA and convert it to cDNA. The gene expression of 14 genes, which play a major role in drug and arachidonic acid metabolism, were measured using quantitative real-time polymerase chain reaction technique.

RESULTS

It was found that the gene expression was downregulated (ANOVA test, -value <0.05) in the livers of UDM mice. The most downregulated genes were , , and with more than 10-fold reduction. The livers of CDM mice showed significantly (-value <0.05) higher levels of mRNA than UDM mice, but still lower than the non-diabetic mice.

CONCLUSION

This study concluded that hepatic gene expression of drug metabolizing and arachidonic acid- enzymes is reduced in insulin-dependent diabetic mice, which can explain, at least in part, the variation in drug and fatty acid metabolism between normal and diabetic patients.