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Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice
文献类型:期刊论文
作者 | Xiao, Fei; Yu, Junjie; Guo, Yajie; Deng, Jiali; Li, Kai; Du, Ying; Chen, Shanghai(陈上海); Zhu, Jianmin; Sheng, Hongguang; Guo, Feifan(郭非凡) |
刊名 | METABOLISM-CLINICAL AND EXPERIMENTAL |
出版日期 | 2014 |
卷号 | 63期号:6页码:841-850 |
关键词 | Leucine deprivation Valine deprivation Isoleucine deprivation Insulin signaling Glucose metabolism |
通讯作者 | Zhu, JM (reprint author), Shanghai Xuhui Cent Hosp, 966 Huaihai Middle Rd, Shanghai 200030, Peoples R China. |
英文摘要 | Objective. We recently discovered that leucine deprivation increases hepatic insulin sensitivity via general control nondepressible (GCN) 2/mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways. The goal of the present study was to investigate whether the above effects were leucine specific or were also induced by deficiency of other branched chain amino acids including valine and isoleucine. Methods. Following depletion of BCAAs, changes in metabolic parameters and the expression of genes and proteins involved in regulation of insulin sensitivity and glucose metabolism were analyzed in mice and cell lines including human HepG2 cells, primary mouse hepatocytes and a mouse myoblast cell line C2C12. Results. Valine or isoleucine deprivation for 7 days has similar effect on improving insulin sensitivity as leucine, in wild type and insulin-resistant mice models. These effects are possibly mediated by decreased mTOR/S6K1 and increased AMPK signaling pathways, in a GCN2-dependent manner. Similar observations were obtained in in vitro studies. In contrast to leucine withdrawal, valine or isoleucine deprivation for 7 days significantly decreased fed blood glucose levels, possibly due to reduced expression of a key gluconeogenesis gene, glucose-6-phosphatase. Finally, insulin sensitivity was rapidly improved in mice 1 day following maintenance on a diet deficient for any individual BCAAs. Conclusions. Our results show that while improvement on insulin sensitivity is a general feature of BCAAs depletion, individual BCAAs have specific effects on metabolic pathways, including those that regulate glucose level. These observations provide a conceptual framework for delineating the molecular mechanisms that underlie amino acid regulation of insulin sensitivity. (C) 2014 Elsevier Inc. All rights reserved. |
类目[WOS] | Endocrinology & Metabolism |
研究领域[WOS] | Endocrinology & Metabolism |
关键词[WOS] | DIET-INDUCED OBESITY ; GENE-EXPRESSION ; KINASE ; RESISTANCE ; LEUCINE ; LIVER ; HOMEOSTASIS ; ISOLEUCINE ; PATHWAY ; MUSCLE |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000336640100013 |
公开日期 | 2016-02-26 |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/426] |
专题 | 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,Yu, Junjie,Guo, Yajie,et al. Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice[J]. METABOLISM-CLINICAL AND EXPERIMENTAL,2014,63(6):841-850. |
APA | Xiao, Fei.,Yu, Junjie.,Guo, Yajie.,Deng, Jiali.,Li, Kai.,...&Guo, Feifan.(2014).Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice.METABOLISM-CLINICAL AND EXPERIMENTAL,63(6),841-850. |
MLA | Xiao, Fei,et al."Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice".METABOLISM-CLINICAL AND EXPERIMENTAL 63.6(2014):841-850. |
入库方式: OAI收割
来源:上海营养与健康研究所
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