阿托伐他汀对db/db糖尿病小鼠胰岛功能的影响

Effects of atorvastatin on islet function in db/db mice

目的探讨阿托伐他汀对db/db糖尿病小鼠糖代谢、胰岛分泌功能的影响。方法 10只db/db糖尿病小鼠随机均分为A1组和A2组,10只db/m小鼠随机均分为B1组和B2组。A1、B1组给予阿托伐他汀10mg·kg-1·d-1灌胃,A2、B2组给予生理盐水灌胃。每周监测体重和血糖,8周后行腹腔葡萄糖耐量试验,采用体外离体胰岛灌流系统评价胰岛分泌功能,Western blot法分析胰岛内葡萄糖激酶的表达。结果 A1、B1组空腹血糖分别高于A2、B2组(P<0.05),葡萄糖耐量及胰岛素第一时相分泌低于A2、B2组(P<0.05),A1组胰岛内葡萄糖激酶表达水平较A2组显著下降(P<0.05)。结论阿托伐他汀使db/db糖尿病小鼠胰岛β细胞第一时相分泌功能降低,从而导致糖耐量受损;这可能与抑制胰岛内葡萄糖激酶的表达有关。

Objective To explore the effects of atorvastatin on blood glucose（BG） metabolism and islet function in db/db mice. Methods Ten db/db mice were equally randomized into groups of A1 and A2, and 10 db/misty mice were equally randomized into groups of B1 and ]32. Atorvastatin 10 mg ·kg^-1·d^-1 was given by gastric gavage for 8 weeks in groups of A1 and B1 and placebo was used in groups of A2 and B2 as the controls. Body weight and BG were measured weekly. At the end of treatment,intraperitoneal glucose tolerance test was performed and glueokinase（GCK） was detected by Western bolt. Results Fasting BG in groups of A1 and B1 was higher than that in groups of A2 and B2（P〈0. 05）. The glucose tolerance and insulin secretion were lower in groups of A1 and B1 than those in groups of A2 and B2（P〈0. 05）. The expression of GCK in the islet was lower in group A1 than that in group A2 （P〈0. 05 ）. Conclusion Atorvastatin decreases insulin secretion of the pancriatic islet in the first-phase,which leads to a decreased glucose intolerance and may be related to a decreased expression of GCK.