LRP6 Bidirectionally Regulates Insulin Sensitivity through Insulin Receptor and S6K Signaling in Rats with CG-IUGR

作     者：Xue-mei XIE Qiu-li CAO Yu-jie SUN Jie ZHANG Kai-li LIU Ying-fen QIN Wen-jun LONG Zuo-jie LUO Xiao-wei LI Xing-huan LIANG Guan-dou YUAN Xiao-ping LUO Xiu-ping XUAN Xue-mei XIE;Qiu-li CAO;Yu-jie SUN;Jie ZHANG;Kai-li LIU;Ying-fen QIN;Wen-jun LONG;Zuo-jie LUO;Xiao-wei LI;Xing-huan LIANG;Guan-dou YUAN;Xiao-ping LUO;Xiu-ping XUAN

作者机构：Department of Endocrinologythe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of PediatricsTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Division of Hepatobiliary Surgerythe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China 

出 版 物：《Current Medical Science》 (当代医学科学（英文）)

年 卷 期：2023年第43卷第2期

页      面：274-283页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82001651 and No.81660268) 

主　　题：intrauterine growth restriction followed by postnatal catch-up growth insulin signaling lipoprotein receptor-related protein 6 Wnt signaling mammalian target of rapamycin/S6 kinase signaling 

摘      要：Objective Intrauterine growth restriction followed by postnatal catch-up growth(CG-IUGR)increases the risk of insulin resistance-related ***-density lipoprotein receptor-related protein 6(LRP6)plays a substantial role in glucose ***,whether LRP6 is involved in the insulin resistance of CG-IUGR is *** study aimed to explore the role of LRP6 in insulin signaling in response to *** The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size *** mRNA and protein expression of the components in the insulin pathway,LRP6/β-catenin and mammalian target of rapamycin(mTOR)/S6 kinase(S6K)signaling,was *** tissues were immunostained for the expression of LRP6 andβ-***6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin *** Compared with the control rats,CG-IUGR rats showed higher homeostasis model assessment for insulin resistance(HOMA-IR)index and fasting insulin level,decreased insulin signaling,reduced mTOR/S6K/insulin receptor substrate-1(IRS-1)serine307 activity,and decreased LRP6/β-catenin in the liver *** knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age(AGA)rats led to reductions in insulin receptor(IR)signaling and mTOR/S6K/IRS-1 serine307 *** contrast,LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 *** LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways,IR and mTOR-S6K ***6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.