“柔肌顺膵饮”代谢物LysoPC(18:0)介导PI3K/AKT/GSK-3β信号通路改善骨骼肌细胞胰岛素抵抗  

LysoPC(18:0),a metabolite of Roujishuntang Drink,improving insulin resistance of skeletal muscle cells through PI3K/AKT/GSK-3βsignaling pathway

作　　者：蔡之幸 朱丹阳[1] 陈莉莉 陈越 CAI Zhi-xing;ZHU Dan-yang;CHEN Li-li;CHEN Yue(Department of Traditional Chinese Medicine,Tongren Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200336;Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海交通大学医学院附属同仁医院中医内科,上海200336 [2]上海中医药大学,上海201203

出　　处：《解剖科学进展》2024年第6期589-592,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金青年科学基金(82205041);陈越长宁区名中医工作室(CNMZY-2021005)。

摘　　要：目的探究“柔肌顺膵饮”代谢物LysoPC(18:0)对骨骼肌细胞胰岛素抵抗的改善作用及机制。方法诱导分化后的C2C12细胞分为对照组(Control组)、胰岛素抵抗组(IR组)、低(LysoPC-L)、中(LysoPC-M)和高LysoPC(18:0)剂量组(LysoPC-H组)。检测细胞培养液上清中葡萄糖浓度;RT-qPCR检测细胞中InsR mRNA表达水平;Western blot检测细胞中InsR、MFN1、MFN2、OPA1、DRP1、FIS1、p-PI3K、PI3K、p-AKT、AKT、p-GSK-3β和GSK-3β蛋白表达水平;流式细胞术检测细胞凋亡率。结果棕榈酸处理的骨骼肌细胞培养液上清中葡萄糖浓度较未处理细胞明显升高,细胞中InsR mRNA和蛋白表达水平降低,细胞凋亡率升高,细胞中MFN1、MFN2、OPA1、p-PI3K、p-AKT和p-GSK-3β蛋白表达水平降低,且DRP1、FIS1和GSK-3β蛋白表达水平增加。LysoPC(18:0)降低棕榈酸处理的骨骼肌细胞培养液上清中葡萄糖浓度,增加细胞中InsR mRNA和蛋白表达水平,降低细胞凋亡率,增加细胞中MFN1、MFN2、OPA1、p-PI3K、p-AKT和p-GSK-3β蛋白表达水平并降低DRP1、FIS1和GSK-3β蛋白表达水平。结论“柔肌顺膵饮”代谢物LysoPC(18:0)改善IR骨骼肌细胞胰岛素抵抗和细胞凋亡,促进细胞中线粒体融合并抑制线粒体分裂,其机制与激活PI3K/AKT/GSK-3β信号通路有关。Objective To explore the improving effect and mechanism of LysoPC(18:0),a metabolite of Roujishuntang Drink,on insulin resistance of skeletal muscle cells.Methods The differentiated C2C12 cells were divided into control group(Control group),insulin resistance group(IR group),LysoPC(18:0)low dose group(LysoPC-L group),LysoPC(18:0)middle dose group(LysoPC-M group)and LysoPC(18:0)high dose group(lysopc).The concentration of glucose in the supernatant of cell culture medium was detected.The level of InsR mRNA was detected by RT-qPCR.The expressions of InsR,MFN1,MFN2,OPA1,DRP1,FIS1,p-PI3K,PI3K,p-AKT,AKT,p-GSK-3β and GSK-3β were detected by Western blot.The apoptosis rate was detected by flow cytometry.Results Compared with untreated cells,the concentration of glucose in the supernatant of skeletal muscle cells treated with palmitic acid was significantly higher,the expression levels of InsR mRNA and protein in cells were decreased,the apoptosis rate was increased,the expressions of MFN1,MFN2,OPA1,p-PI3K,p-AKT and p-GSK-3β in cells were decreased,and the expressions of DRP1,FIS1 and GSK-3β were increased.LysoPC(18:0)decreased the glucose concentration in the supernatant of palmitic acid-treated skeletal muscle cells,increased the expression levels of InsR mRNA and protein in cells,decreased the apoptosis rate,increased the expressions of MFN1,MFN2,OPA1,p-PI3K,p-AKT and p-GSK-3βin cells,and decreased the expressions of DRP1,FIS1 and GSK-3β proteins.Conclusion LysoPC(18:0),a metabolite of Roujishuntang Drink,improves insulin resistance and apoptosis of IR skeletal muscle cells,promotes mitochondrion fusion and inhibits mitochondrion division,and its mechanism may be related to the activation of PI3K/AKT/GSK-3β signaling pathway.

关 键 词：LysoPC(18:0) 骨骼肌 胰岛素抵抗 线粒体动力学 PI3K/AKT/GSK-3β信号通路 

分 类 号：R587.2[医药卫生—内分泌]