{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362544420214830592.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2337/db10-1246"}},{"identifier":{"@type":"URI","@value":"https://journals.org/diabetes/diabetes/article-pdf/60/3/746/401407/746.pdf"}},{"identifier":{"@type":"URI","@value":"https://diabetesjournals.org/diabetes/article-pdf/60/3/746/401407/746.pdf"}}],"dc:title":[{"@value":"Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n                  <jats:title>OBJECTIVE</jats:title>\n                  <jats:p>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.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS</jats:title>\n                  <jats:p>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.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS</jats:title>\n                  <jats:p>We show that leucine deprivation improves hepatic insulin sensitivity by sequentially activating general control nonderepressible (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.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS</jats:title>\n                  <jats:p>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.</jats:p>\n               </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382544420214830593","@type":"Researcher","foaf:name":[{"@value":"Fei Xiao"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830602","@type":"Researcher","foaf:name":[{"@value":"Zhiying Huang"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830603","@type":"Researcher","foaf:name":[{"@value":"Houkai Li"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830592","@type":"Researcher","foaf:name":[{"@value":"Junjie Yu"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830601","@type":"Researcher","foaf:name":[{"@value":"Chunxia Wang"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830595","@type":"Researcher","foaf:name":[{"@value":"Shanghai Chen"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830599","@type":"Researcher","foaf:name":[{"@value":"Qingshu Meng"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830598","@type":"Researcher","foaf:name":[{"@value":"Ying Cheng"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830597","@type":"Researcher","foaf:name":[{"@value":"Xiang Gao"}],"jpcoar:affiliationName":[{"@value":"Model Animal Research Center, Nanjing University, Nanjing, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830600","@type":"Researcher","foaf:name":[{"@value":"Jia Li"}],"jpcoar:affiliationName":[{"@value":"National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830596","@type":"Researcher","foaf:name":[{"@value":"Yong Liu"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]},{"@id":"https://cir.nii.ac.jp/crid/1382544420214830594","@type":"Researcher","foaf:name":[{"@value":"Feifan Guo"}],"jpcoar:affiliationName":[{"@value":"Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00121797"},{"@type":"EISSN","@value":"1939327X"}],"prism:publicationName":[{"@value":"Diabetes"}],"dc:publisher":[{"@value":"American Diabetes Association"}],"prism:publicationDate":"2011-02-21","prism:volume":"60","prism:number":"3","prism:startingPage":"746","prism:endingPage":"756"},"reviewed":"false","dc:rights":["http://creativecommons.org/licenses/by-nc-nd/3.0/"],"url":[{"@id":"https://journals.org/diabetes/diabetes/article-pdf/60/3/746/401407/746.pdf"},{"@id":"https://diabetesjournals.org/diabetes/article-pdf/60/3/746/401407/746.pdf"}],"createdAt":"2011-02-01","modifiedAt":"2022-11-02","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004232103264640","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The impact of dietary protein intake on longevity and metabolic health"}]},{"@id":"https://cir.nii.ac.jp/crid/1360846643381462144","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"ATF4 induction through an atypical integrated stress response to ONC201 triggers 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