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Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways

文献类型：期刊论文

作者Xiao, Fei1; Huang, Zhiying1; Li, Houkai1; Yu, Junjie1; Wang, Chunxia1; Chen, Shanghai1; Meng, Qingshu1; Cheng, Ying1; Gao, Xiang3; Li, Jia2
刊名DIABETES
出版日期2011-03
卷号60期号:3页码:746-756
ISSN号0012-1797
DOI10.2337/db10-1246
文献子类Article
英文摘要OBJECTIVE-We have previously shown that serum insulin levels decrease threefold and blood glucose levels remain normal in mice fed a leucine-deficient diet, suggesting increased insulin sensitivity. The goal of the current study is to investigate this possibility and elucidate the underlying cellular mechanisms. RESEARCH DESIGN AND METHODS-Changes in metabolic parameters and expression of genes and proteins involved in regulation of insulin sensitivity were analyzed in mice, human HepG2 cells, and mouse primary hepatocytes under leucine deprivation. RESULTS-We show that leucine deprivation improves hepatic insulin sensitivity by sequentially activating general control non-derepressible (GCN)2 and decreasing mammalian target of rapamycin/S6K1 signaling. In addition, we show that activation of AMP-activated protein kinase also contributes to leucine deprivation-increased hepatic insulin sensitivity. Finally, we show that leucine deprivation improves insulin sensitivity under insulin-resistant conditions. CONCLUSIONS-This study describes mechanisms underlying increased hepatic insulin sensitivity under leucine deprivation. Furthermore, we demonstrate a novel function for GCN2 in the regulation of insulin sensitivity. These observations provide a rationale for short-term dietary restriction of leucine for the treatment of insulin resistance and associated metabolic diseases. Diabetes 60:746-756, 2011
WOS关键词DIET-INDUCED OBESITY ; AMINO-ACID AVAILABILITY ; GENE-EXPRESSION ; SERINE PHOSPHORYLATION ; RECEPTOR SUBSTRATE-1 ; METABOLIC SYNDROME ; MAMMALIAN TARGET ; LIPID-METABOLISM ; SKELETAL-MUSCLE ; MTOR PATHWAY
资助项目Ministry of Science and Technology of China[2009CB919001] ; Ministry of Science and Technology of China[2010CB912502] ; National Natural Science Foundation[30871208] ; National Natural Science Foundation[30890043] ; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[SIBS2008006] ; Science and Technology Commission of Shanghai Municipality[08dj1400601] ; Clinical Research Center, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[CRC2010005] ; Key Program of Shanghai Scientific and Technological Innovation Action Plan[10JC1416900] ; CAS-Pfizer[Pfizer-SIBS2 01002] ; Chinese Academy of Sciences[00000000] ; Shanghai Municipality[08PJ1410700]
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:000288060300009
出版者AMER DIABETES ASSOC
源URL[http://119.78.100.183/handle/2S10ELR8/278593]  
专题国家新药筛选中心
药物安全性评价中心
通讯作者Guo, Feifan
作者单位1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 200031, Peoples R China
3.Nanjing Univ, Model Anim Res Ctr, Nanjing 210008, Peoples R China;
推荐引用方式
GB/T 7714		 Xiao, Fei,Huang, Zhiying,Li, Houkai,et al. Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways[J]. DIABETES,2011,60(3):746-756.
APA Xiao, Fei.,Huang, Zhiying.,Li, Houkai.,Yu, Junjie.,Wang, Chunxia.,...&Guo, Feifan.(2011).Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways.DIABETES,60(3),746-756.
MLA Xiao, Fei,et al."Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways".DIABETES 60.3(2011):746-756.

入库方式： OAI收割

来源：上海药物研究所

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