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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, Fei; Huang, Zhiying; Li, Houkai; Yu, Junjie; Wang, Chunxia; Chen, Shanghai（陈上海）; Meng, Qingshu; Cheng, Ying; Gao, Xiang; Li, Jia |
| 刊名 | DIABETES
 |
| 出版日期 | 2011 |
| 卷号 | 60期号:3页码:746-756 |
| 通讯作者 | Guo, FF (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China. |
| 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 |
| 类目[WOS] | Endocrinology & Metabolism |
| 研究领域[WOS] | Endocrinology & Metabolism |
| 关键词[WOS] | DIET-INDUCED OBESITY ; AMINO-ACID AVAILABILITY ; GENE-EXPRESSION ; SERINE PHOSPHORYLATION ; RECEPTOR SUBSTRATE-1 ; METABOLIC SYNDROME ; MAMMALIAN TARGET ; LIPID-METABOLISM ; SKELETAL-MUSCLE ; MTOR PATHWAY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000288060300009 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/288]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 中国科学院上海生命科学研究院营养科学研究所_代谢的遗传与营养调控研究组 |
| 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：上海营养与健康研究所
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