尼古丁增强大鼠胰岛素敏感性

Nicotine enhances insulin sensitivity in rats

目的研究尼古丁对大鼠胰岛素敏感性的影响及其与过氧化酶体增殖物激活受体(PPAR-γ)的关系。方法将10～11周龄的雄性SD大鼠随机分为生理盐水组和尼古丁组,两组又各分为3个亚组(1周、3周及6周组),分别给生理盐水(生理盐水组)或3mg·kg-1·d-1尼古丁(尼古丁组)1周、3周、6周。各组均为皮下注射给药,每天1次。每周记录大鼠体质量变化。给药3周、6周后进行胰岛素耐量试验;给药1周、3周和6周后检测血清生化指标;给药6周后对各部位脂肪称量,并通过蛋白质印迹方法检测PPAR-γ蛋白在内脏脂肪和皮下脂肪的表达情况。结果尼古丁给药后大鼠体质量增幅减缓;胰岛素耐量试验显示给药3周、6周后胰岛素敏感性增强(P<0.05);3周后血清三酰甘油明显下降(P<0.01);6周后血清胰岛素敏感性相关指数明显增加(P<0.05);给药6周后皮下脂肪、内脏脂肪的绝对质量和相对质量均下降(P<0.01),且内脏脂肪下降幅度大于皮下脂肪,而内脏脂肪和皮下脂肪PPAR-γ蛋白表达不改变。结论尼古丁可增强大鼠胰岛素敏感性,该作用部分与尼古丁减少脂肪组织,尤其是内脏脂肪组织量及减少血清三酰甘油水平有关,而与脂肪组织中PPAR-γ表达无关。

Objective To investigate the effect of nicotine on insulin sensitivity in rats and its relationship with PPAR-γ.Methods Male Sprague-Dawley rats（10-11 weeks old） were randomly divided into saline group and nicotine group,and the two groups were further divided into 3 subgroups：1 week,3 weeks,and 6 weeks subgroups according to the time they were treated by different agents.Rats were subcutaneously injected with saline（saline group） daily or nicotine（3 mg·kg-1·d-1,nicotine group） for 1 week,3 weeks,and 6 weeks.The body weights of animals were recorded on a weekly basis.Insulin tolerance tests were performed at 3 weeks and 6 weeks after treatment,and the serum parameters were determined at 1 week,3 weeks,and 6 weeks after drug administration.At the end of the experiment,fat tissue weights of different body parts were weighed,and PPAR-γ expression in the subcutaneous fat and visceral fat was detected by Western blotting analysis.Results The body weight increase of rats was inhibited after nicotine treatment.Insulin sensitivity of rats was significantly enhanced 3 weeks and 6 weeks after nicotine treatment（P0.05）,serum triglyceride level was decreased significantly at 3 weeks after nicotine treatment（P0.01）,insulin sensitivity indices were increased after 6 weeks（P0.05）,and both the weight and relative weight of subcutaneous and visceral fat tissues were significantly decreased 6 weeks after nicotine treatment（P0.01）,with the visceral fat decreased more severely than that of the subcutaneous fat.PPAR-γ expressions in the subcutaneous fat and visceral fat tissues were not significantly different between saline and nicotine treated groups.Conclusion Nicotine can improve insulin sensitivity in rats,which is partly due to the fact that nicotine can decrease the serum triglyceride levels and fat tissue,especially the visceral fat tissue,but has no relation with PPAR-γ protein expression in fat tissue.