Related Experiment Video
Updated: Aug 9, 2026
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Regulation of renal cytochrome P450s by thyroid hormone in diabetic rats
S Imaoka1, M Nakamura, T Ishizaki
1Laboratory of Chemistry, Osaka City University Medical School, Japan.
Abstract:
Effects of thyroid hormone treatment on renal P450 expression in the diabetic rats were investigated. Diabetes produced by streptozotocin induced CYP4A2 and P450 K-2 (similar form with CYP2C23) but not P450 K-4 (similar form with CYP4A8) and induced lauric acid hydroxylation activity. The serum thyroid hormone level was decreased with diabetes. Treatment of diabetic rats with thyroid hormone (T3) as well as with insulin reversed the increase in the levels of CYP4A2 and P450 K-2. Thyroidectomy also induced CYP4A2 and P450 K-2 in the rat kidney. The increase was reversed by treatment of thyroidectomized rats with T3. These findings suggest that expression of CYP4A2 and P450 K-2 in rat kidney is suppressively regulated by thyroid hormone and the decrease in thyroid hormone level in the diabetic state affects the levels of CYP4A2 and P450 K-2.
Insights
Thyroid hormone (T3) levels decrease in diabetic rats, increasing renal CYP4A2 and P450 K-2 expression. T3 treatment or insulin reversed these changes, suggesting thyroid hormone suppresses these P450s.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is associated with altered xenobiotic metabolism.
- Renal cytochrome P450 (CYP) enzymes play a role in drug and endogenous compound metabolism.
- Thyroid hormones influence various metabolic processes, but their effect on renal CYP expression in diabetes is not fully understood.
Purpose of the Study:
- To investigate the impact of thyroid hormone levels on renal CYP4A2 and P450 K-2 expression in diabetic rats.
- To determine if thyroid hormone treatment can modulate CYP expression altered by diabetes.
Main Methods:
- Diabetes was induced in rats using streptozotocin.
- CYP4A2, P450 K-2, and P450 K-4 expression levels were measured.
- Lauric acid hydroxylation activity was assessed.
- Serum thyroid hormone levels were analyzed.
- Effects of thyroid hormone (T3) and insulin treatment on diabetic rats were evaluated.
- Effects of thyroidectomy and subsequent T3 treatment were examined.
Main Results:
- Diabetes induced renal CYP4A2 and P450 K-2, along with lauric acid hydroxylation activity.
- Serum thyroid hormone levels were reduced in diabetic rats.
- T3 or insulin treatment reversed the diabetes-induced increase in CYP4A2 and P450 K-2.
- Thyroidectomy increased CYP4A2 and P450 K-2, an effect reversed by T3 administration.
Conclusions:
- Renal CYP4A2 and P450 K-2 expression are negatively regulated by thyroid hormone.
- The reduced thyroid hormone levels in diabetes contribute to the induction of these specific renal CYPs.
- Thyroid hormone replacement therapy may offer a strategy to normalize altered renal CYP expression in diabetic conditions.
