Mifepristone Improves Hyperglycemia in Diabetic Rats by Regulating Glucocorticoid Receptor Expression
10.3870/yydb.2014.10.006
- VernacularTitle:米非司酮基于糖皮质激素受体调节糖尿病大鼠高血糖的作用机制
- Author:
Xiaoli WANG
;
Jun ZHOU
;
Maoxing LI
;
Jianguo QIU
;
Zhengping JIA
;
Ruxue ZHANG
- Publication Type:Journal Article
- Keywords:
Mifepristone;
Hyperglycemia;
Glucocorticoid receptor;
Diabetes mellitus,type 2
- From:
Herald of Medicine
2014;(10):1278-1283
- CountryChina
- Language:Chinese
-
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 (P<0. 01),FBG was increased significantly (P<0. 01),organ index was increased significantly (P<0. 05), CRH,ACTH,CORT,INS and ALD were increased and the expression of GR mRNA in hippocampus was decreased (P<0. 01) in the model control group. Compared with model control group,body weight increased in MIF-M and MIF-H groups after administration for 14 days (P<0. 01). FBG was decreased in MIF-M group 1 to 4 weeks after administration,with significant difference (P<0. 05) at 4th week. The kidney index was decreased in MIF-M and MIF-H groups (P<0. 01,P<0. 05). CRH,ACTH and CORT were increased,ALD level was decreased in MIF-L group,CRH,ACTH,CORT and ALD were decreased,INS level was increased in MIF-M and MIF-H groups,without statistically significant differences (P>0. 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.
