Mifepristone Improves Hyperglycemia in Diabetic Rats by Regulating Glucocorticoid Receptor Expression / 医药导报

ABSTRACT

Objective To observe the effect of mifepristone (MIF) on the level of corticotropin releasing hormone (CRH),adrenocorticotropic hormone (ACTH),corticosterone (CORT),insulin (INS) and aldosterone (ALD) in plasma and expression of glucocorticoid receptor (GR) mRNA in hippocampus in type 2 diabetic rats and to discuss the effect and mechanism by which mifepristone improves hyperglycemia. Methods Type 2 diabetes mellitus model was induced by high-fat diet plus intragastric administration of low dose streptozotocin (30 mg·kg-1 ). Rats were randomly divided into normal control group,model control group,positive control (MET) (metformin hydrochloride 200 mg·kg-1 ·d-1 ) group,mifepristone low dose (MIF-L) (10 mg·kg-1 ·d-1 ),medium dose (MIF-M) (25 mg·kg-1 ·d-1 ) and high dose (MIF-H) (50 mg·kg-1 ·d-1 ) groups. The normal control group and model control group were given distilled water. Fasting blood glucose (FBG) was measured once a week. The rats were decapitated after five weeks. Organ index, corticotropin release hormone ( CRH), adrenocorticotropic hormone (ACTH),corticosterone(CORT),insulin(INS) and aldosterone(ALD) levels were measured. The expression of GR mRNA in hippocampus was measured by using real-time PCR. Results Compared with the normal control group, body weight was decreased significantly (P0. 05). Relative expression of GR mRNA was significantly increased in MIF-L,MIF-M and MIF-H groups (all P <0. 01). Conclusion Hyperglycemia in type 2 diabetic rats can be improved by MIF. The possible mechanism may be related to regulating the HPA axis through inhibiting GR.