基于FOXO1/PINK1信号通路探讨线粒体自噬在胰岛细胞衰老促进肥胖型糖尿病中的机制  

The mechanism of mitochondrial autophagy in islet cell aging promoting obesity diabetes mellitus based on FOXO1/PINK1 signaling pathway

作　　者：黄敏 魏若萱 宋惠杰 HUANG Min;WEI Ruoxuan;SONG Huijie(Department of Endocrinology,Wuhan Hospital of Integrated Traditional Chinese and Western Medicine,Wuhan First Hospital,Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]武汉市中西医结合医院·武汉市第一医院·华中科技大学同济医学院附属中西医结合医院内分泌科,湖北武汉430022

出　　处：《西部医学》2024年第8期1137-1142,共6页Medical Journal of West China

基　　金：湖北省自然科学基金项目(ZK20210152)。

摘　　要：目的基于FOXO1/PINK1信号通路介导的线粒体自噬,探究胰岛细胞衰老在肥胖型糖尿病中的可能作用机制。方法将30只SD大鼠随机分为对照组、肥胖型糖尿病组、FOXO1激活组,每组10只。观察记录各组大鼠的一般状态,葡萄糖检测试剂盒检测各组大鼠血糖水平,ELISA试剂盒、透射电镜检测并观察各组大鼠胰岛素水平,RT-qPCR、Western blot检测各组大鼠胰脏组织中自噬通路相关蛋白FOXO1、PINK1、Parkin、LC3Ⅱ及衰老相关蛋白p16、p21、Rb mRNA及蛋白水平。结果与对照组相比,肥胖型糖尿病组大鼠胰脏组织中FOXO1、PINK1、Parkin、LC3ⅡmRNA、蛋白水平减少(P<0.05)。与对照组相比,肥胖型糖尿病组大鼠每日摄食量、饮水量及尿量均增加(P<0.05);与肥胖型糖尿病组大鼠相比,FOXO1激活组大鼠每日摄食量、饮水量及尿量均减少(P<0.05)。与对照组相比,肥胖型糖尿病组大鼠空腹血糖、空腹胰岛素含量增加,胰岛素敏感指数减少(P<0.05);与肥胖型糖尿病组大鼠相比,FOXO1激活组大鼠空腹血糖、空腹胰岛素含量减少,胰岛素敏感指数增加(P<0.05)。透射电镜结果显示,与对照组相比,肥胖型糖尿病组大鼠胰岛β细胞中胰岛素颗粒数量显著增加;与肥胖型糖尿病组大鼠相比,FOXO1激活组大鼠胰岛β细胞中胰岛素颗粒数量显著减少。与对照组相比,肥胖型糖尿病组大鼠胰脏组织中FOXO1、PINK1、Parkin、LC3ⅡmRNA水平减少(P<0.05);与肥胖型糖尿病组大鼠相比,FOXO1激活组大鼠FOXO1、PINK1、Parkin、LC3ⅡmRNA水平增加(P<0.05)。与对照组相比,肥胖型糖尿病组大鼠胰脏组织中衰老相关基因p16、p21、Rb mRNA、蛋白水平增加(P<0.05);与肥胖型糖尿病组大鼠相比,FOXO1激活组大鼠p16、p21、Rb mRNA、蛋白水平减少(P<0.05)。结论激活FOXO1可激活肥胖型糖尿病大鼠胰腺组织中的线粒体自噬,下调胰岛细胞衰老相关基因,改善大鼠的一般状态肌血糖指标,这可�Objective Based on mitochondrial autophagy mediated by FOXO1/PINK1 signaling pathway,the possible mechanism of islet cell senescence in obese diabetes mellitus was explored.Methods Thirty SD rats were randomly divided into control group,obesity diabetes group and FOXO1 activation group,with 10 rats in each group.During this period,the general state of rats in each group was observed and recorded.Glucose level of rats in each group was detected by Sugar test kit,and insulin level of rats in each group was detected by ELISA kit and transmission electron microscope.The mRNA and protein levels of autophagy pathway related proteins FOXO1,PINK1,Parkin,LC3Ⅱand aging related proteins p16,p21 and Rb in the pancreatic tissues of rats in each group were detected by RT-qPCR and Western blotting.Results Compared with the control group,the mRNA and protein levels of FOXO1,PINK1,Parkin,LC3Ⅱin pancreatic tissue of rats with obesity diabetes group decreased(P<0.05).Compared with the control group,the daily food intake,water intake and urine volume of rats in the obese diabetes group were increased(P<0.05).Compared with obese diabetic rats,the daily food intake,water intake and urine volume of rats in FOXO1-activated group were decreased(P<0.05).Compared with the control group,fasting blood glucose and fasting insulin contents were increased and insulin sensitivity index was decreased(P<0.05).Compared with the obese diabetic group,the contents of fasting glucose and fasting insulin in FOXO1-activated group were decreased,and the insulin sensitivity index was increased(P<0.05).The results of transmission electron microscopy showed that compared with the control group,the number of insulin particles in the islet beta cells of the obese diabetic group was significantly increased.Compared with the obese diabetic rats,the number of insulin particles in the islet beta cells of the FOXO1-activated rats was significantly decreased.Compared with the control group,the mRNA levels of FOXO1,PINK1,Parkin and LC3Ⅱin pancreatic tissue of r

关 键 词：肥胖型糖尿病 FOXO1/PINK1信号通路 线粒体自噬 胰岛细胞衰老 

分 类 号：R587.1[医药卫生—内分泌]