雌激素在低雄激素雄性大鼠发生胰岛素抵抗中的作用

Effect of estrogen on insulin resistance in male rats with low serum testosterone levels

目的:观察芳香化酶抑制剂来曲唑抑制正常及低雄激素雄性大鼠体内雌激素后血糖和胰岛素的变化,探讨雌激素在低雄激素雄性大鼠胰岛素抵抗发生中的作用。方法:成年雄性大鼠32只均分为四组:对照组、睾丸切除组、来曲唑组、睾丸切除加来曲唑组。采用来曲唑或双蒸水处理4周后,测量大鼠体重,空腹12小时取血检测总睾酮(TTs)、雌二醇(E2)、空腹血糖(FBG)、空腹胰岛素(FINS),计算稳态模型胰岛素抵抗指数(HOMA-IR)。结果:四组大鼠体重无显著差异。与对照组比较,睾丸切除组及睾丸切除加来曲唑组血清TTs水平明显降低(P<0.05～<0.01),FBG、FINS、HOMA-IR水平显著升高(P<0.05)。睾丸切除加来曲唑组较睾丸切除组E2、雌激素/睾丸酮(E2/T)比值显著降低(P<0.05),FBG、HOMA-IR水平显著升高(P<0.05),FINS水平无显著差异。结论:雄激素水平降低致雄性大鼠空腹血糖和胰岛素水平升高,胰岛素抵抗;在低雄激素水平的基础上,雄性大鼠体内雌激素水平降低,可导致胰岛素抵抗指数进一步升高。提示雌激素也参与了雄激素缺乏大鼠代谢综合征的发病过程。

Objective： To determine whether insulin resistance in male rats with low serum testosterone level related to low serum estrogen level. Methods： A total of 32 adult male rats were divided into 4 groups equally. Orchiectomy was performed on rats of group B an D. Rats of group C and D were given the aromatase inhibiton letrozole （5mg/kg · d） by intragastric administration daily for 4 weeks. Group A and 13 received distilled water as control. After 4 weeks, body weight and serum levels of total testosterone （TTs）, estradiol （E2）, fasting glucose （FBG）, fasting insulin （FINS） were measured, and the homeostasis model assessment for insulin resistance （HOMA-IR） was calcu lated. Results： No significant difference was observed on the body weight among the four groups （P〉0. 05）. The serum levels of TTs decreased and FBG, FINS, HOMA-IR levels increased significantly in group B and D compared with group A （P〈0.05）. The E2 and E2/T levels significantly decreased （P〈0.05-0. 01） in group D, compared with group B. There were higher FBG, HOMA-IR levels in group D compared with group B （P〈0. 05）, but no change was observed on FBG between these two groups. Conclusion： Low serum testosterone levels may induce insulin resistance in male rats. Such disorder should be more severe by cutting down the estrogen level in male rats with low level of testosterone. These data indicate that insufficient estrogen may contribute to the pathogenesis of metabolic syndrome in rats with low serum testosterone Levels.