生长激素对肝脏胰岛素信号的时间程序性效应  

The time proceeding effect of growth hormone on liver insulin signaling

作　　者：王楚琼[1] 朱孔芹[2] 叶火旺 赵巧飞 南清振[2] 

机构地区：[1]深圳市龙岗中心医院消化内科,广东省518116 [2]南方医科大学南方医院消化内科,广州市510515

出　　处：《实用医学杂志》2015年第2期194-197,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:81170743)

摘　　要：目的:生长激素和胰岛素间的相互作用关系有待于进一步的研究。本研究首次同时检查在个体(小鼠)和细胞培养水平上,生长激素作用对肝脏胰岛素信号的时间效应关系。方法:小鼠分别注射重组人生长激素(rh GH)30 min,4 h,3周,取肝组织,提取蛋白,western blot检测胰岛素信号变化。人肝癌细胞系Hep G2分别给予rh GH刺激30 min,4 h,裂解前10 min再分别予胰岛素刺激,裂解细胞提取蛋白,western blot检测胰岛素信号变化。结果:rh GH预刺激小鼠30 min后,肝组织的基础Akt磷酸化水平明显升高,处死前10 min胰岛素刺激产生的Akt磷酸化水平则没有变化;rh GH预刺激小鼠4 h后,无论是肝组织的基础Akt磷酸化水平还是处死前10 min胰岛素刺激产生的Akt磷酸化水平都没有变化;而rh GH预刺激小鼠3周时,无论是肝组织的基础Akt磷酸化水平还是处死前10 min胰岛素刺激产生的Akt磷酸化水平都降低。然而在Hep G2细胞培养试验中,4 h生长激素预刺激则足以导致Akt磷酸化的抑制。结论:生长激素对胰岛素信号的作用规律是,急性(短时)生长激素作用时可产生正向激活作用;随着生长激素作用时间的延长,其效应逐渐变为抑制作用,也即Akt的磷酸化水平从作用开始时(几十分钟时间内)升高,随着时间延长后逐渐降低。但这个变化过程在动物水平上的表现远比细胞水平的慢,这可能体现了生理情况下多信号通路间相互作用的复杂性。Objective To examine the time effect relationship of GH on insulin signaling both in vivo and in vitro. Methods Mice were intraperitoneal injected with recombinant human growth hormone （rhGH） for 30 min, 4 hours and 3 weeks, respectively before liver being removed, protein isolated, and insulin signaling examined. Similarly, HepG2 cells were treated with rhGH for 30 rain and 4 hours. Thereafter, cells were harvested after 10 min insulin stimulation before examination. Results Basic line phosphor-Akt was activated in mice after 30 min rhGH pre-challenge and in the 10 min insulin stimulated group the phospho-Akt did not change. Both 30 min group or 10 rain group showed no phospho-Akt change after 4 hours＇ rhGH pre-challenge and both were inhibited after 3 weeks＇ rhGH pre-treatment. However in HepG2 cells, 4 hours＇ rhGH treatment was enough to cause inhibition of phospho-Akt. Conclusion Short-term GH challenge activats insulin signaling and this stimulating effect turns to suppressive when the treatment period is extended. That is, short-term rhGH activated phosphor-Akt signals, and gradual changes turned inhibiting as time goes by. The process is much slower in vivo compared to that of in vitro, which may reflect the complexity of the interaction between signal pathways in physiological environment.

关 键 词：生长激素 PI3K/AKT 肝脏 细胞 胰岛素抵抗 

分 类 号：R335.6[医药卫生—人体生理学]