Abstract: Objective To explore the effects of H8, an inhibitor of 11β-HSD1, on insulin sensitivity in db/db mice. Methods A total of 40 db/db mice were divided into 5 groups: db/db model group(Dia), rosiglitazone treatment group(Ros), curcumin treatment group(Cur), curcumin analogues H8 treatment group(H8), and db/m control group(Con). H8 was intragastriclly administered once per day for 6 weeks, and then oral glucose tolerance test(OGTT)and intraperitoneal insulin tolerance test(IPITT)were performed at the end of the 6th week. Fasting blood glucose levels, collected from the tail vein, were measured in 0th, 1th, 3th, and 6th week. At the end of the experiment, the inner canthus vein blood was collected to examine HOMA-RI index. The activity of 11β-HSD1 in liver and adipocytes and the level of glucocorticoid in serum were detected with enzyme method and ELISA, respectively. Results The results of OGTT showed that the blood glucose level was significantly reduced in the Ros group and H8 group than in the Dia group. The IPITT results revealed that the blood glucose level was significantly reduced in the Ros group and H8 group than in the Dia group. Fasting blood glucose level of H8 group was significantly lower than that of Dia group from the 1th to 6th week after the treatment. The HOMA-IR indicator of the Ros group, Cur group and H8 group was significantly lower compared with that of the Dia group(P<0.001). Compared with Dia group, H8 had 山 东 大 学 学 报 (医 学 版)55卷10期 -李洪志,等.11β-HSD1抑制剂改善db/db小鼠胰岛素敏感性的实验研究 \=-significantly inhibited 11β-HSD1 activity in liver(P<0.01)and adipocytes(P<0.01), and reduced level of GC(P<0.001). Conclusion H8, an 11β-HSD1 inhibitor, could reduce the hepatic GC level in db/db mice, thereby increasing the sensitivity of insulin.

Key words: Insulin resistance, db/db mouse, 11β-HSD1 inhibitor