AMPK/mTOR信号通路在DIO与DR大鼠胰腺中的表达

The role of mTOR signaling pathway in pancreas of Diet- Induced Obese(DIO) and diet resistance DR rats

目的通过比较DIO大鼠和DR大鼠胰腺中AMPK/mTOR通路的变化探讨其对整个机体能量和代谢过程中的作用。方法建立食源性肥胖大鼠模型:100只体重均衡的大鼠随机分为①高脂饮食组(n=80)和②对照组(n=20),前者14周后根据体重分为肥胖(DIO)和肥胖抵抗(DR)两个亚组。通过免疫组化和免疫荧光的方法检测DIO和DR大鼠胰腺中AMPK/mTOR通路的表达变化。结果①14周后,高脂饮食组体重高于对照组体重(P<0.001),DIO与DR组之间体重相比有明显差异(P<0.001);②与DIO组相比,DR组大鼠胰腺的AMPK表达水平降低,mTOR下游的两个经典靶标S6K和4E-BP1表达水平明显增加。结论 DR大鼠胰腺AMPK水平降低,S6K和4E-BP1水平升高,说明AMPK抑制mTOR通路功能下降,导致胰岛α细胞分泌胰高血糖素增加,这可能是DR大鼠维持正常体重的原因之一。

Objective To explore the effects involved in body energy balance and metabolism by comparing the expression changes of AMPK/roTOR pathway in panereas between DIO and DR rats. Methods To establish obe- sity animal models 100 rats, which are matched in body weight are divided randomly into two groups 1 ）high fat diet group （n = 80） and 2 ）control group （n = 20）. According to body weight, rats in the first goup are divided in- to DIO and DR after 14 weeks of high fat diet. Compare the activity of AMPK/mTOR pathway in pancreas of DIO and DR rats by using the methods of immunohistochemistry and immunofluorescence. Results 1 ） After 14 weeks, body weight of rats in high fat diet group exceed control group（P 〈0. 001 ）. There is a statistically significant on body weight between DIO and DR rats（P 〈0. 001 ）. 2）Compare with DIO rats, signals of AMPK in pancreas of DR rats are less active, while S6K and 4E - BPI are more active. Conclusion Pancreas of DR rats have less ac- tive of AMPK and more active of mTOR pathway, means that the function of AMPK inhibiting mTOR pathway is declined in DR rats whose α cells of pancreas secrete more glucagons than DIO rats. Maybe this is one of the reasons for maintaining healthy body weight in DR rats.