Abstract:

To observe the influence  of  novel liver X receptor (LXR) agonist ATI-829 on the blood glucose level,body weight and dietary consumption of type 2 diabetes mellitus KKAy mice and  the incidence of type 1 diabetic NOD mice, and to provide evidence for clinical application.Methods Fifteen 12-week male type 2 diabetes mellitus KKAy mice were randomly divided into vehicle control group,pioglitazone treatment group,and ATI-829 treatment group.The mice were treated for 2 weeks, and the  blood glucose levels,body weights,and the dietary consumptions of mice were measured every week.Forty 6-week female type 1 diabetes mellitus NOD mice were divided into vehicle control group,classic LXR agonist T1317 treatment group,and ATI-829 treatment group.The mice were treated for 8 weeks, and the cumulative incidence was  measured every two weeks from 20 to 34 week.Results In type 2 diabetes mellitus mice,after 1 week treatment,the glucose level,body wieght and the dietry consumption of mice in various groups didn’t change significantly compared with those before treatment.After 2 weeks treatment, the blood glucose level of mice in pioglitazone treatment group was decreased from (30.11±3.94) mmol.L^-1 to (14.00±2.78) mmol.L^-1,and the body weight was  increased from (36.96±1.17) g to (41.14±0.99) g,there were significant differences compared with vehicle control group(P<0.05).The blood glucose level of mice  in ATI-829 treatment group was decreased from(33.28±1.89) mmol.L^-1 to (15.89±1.06) mmol.L^-1,there was significant difference compared with vehicle control group(P<0.05);and the body weight was  decreased from (37.82±0.96) g to (37.11±0.26) g,there was no significant difference compared with vehicle control group(P>0.05).The dietary consumption didn’t change significantly in various groups before and after treatment.In type 1 diabetic NOD mice,ATI-829 was able to totally prevent the disease occurrence and the disease incidence in T1317 treatment group rose to 90%,which was 50%  in vehicle control group，there were  significant differences between T1317 group,ATI-829 treatment  group and    vehicle control group(P<0.05).Conclusion The novel   liver X receptor  agonist ATI-829 can decrease the blood glucose levels of type 2 diabetes mellitus mice and avoid body weight gain.Meanwhile,ATI-829 can also decrease the incidence of type 1 diabetes mellitus in mice.