Investigation of the mechanisms of hepatic insul in sensitization by retinoi cacid.

视黄酸致敏肝胰岛素机制的研究。

• 批准号: 23790819
• 负责人: TSUCHIYA Hiroyuki
• 金额: $ 2.66万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790819/
• 关键词: レチノイン酸; タミバロテン; インスリン抵抗性; レプチン; STAT3; 肝臓; NAFLD; NASH; アンチセンスRNA

Based on our original finding, the leptin-dependent hepatic insulinsensitization by retinoid, I investigated its precise mechanisms. It was demonstrated thatretinoid activates hepatic leptin signaling by directly inducing leptin receptor expressionvia retinoid receptor. A synthetic rtinoid, tamibarotene, also showed the same effect,suggesting its potential as a novel insulin-resistance treatment. Moreover, AntiX wasidentified as a target gene of hepatic leptin signaling, and the expression level of AntiX inthe liver was significantly correlated with the pathological status of insulin resistance.

基于我们最初的发现，即类视黄醇对瘦素依赖性肝脏胰岛素增敏作用，我研究了其精确机制。研究表明，类视黄醇通过类视黄醇受体直接诱导瘦素受体表达，从而激活肝脏瘦素信号传导。一种合成类维生素A，他米巴罗汀，也显示出相同的效果，表明其作为新型胰岛素抵抗治疗的潜力。此外，AntiX被确定为肝脏瘦素信号传导的靶基因，肝脏中AntiX的表达水平与胰岛素抵抗的病理状态显着相关。

项目成果

Retinoids ameliorate insulin resistance in a leptin-dependent manner in mice

• DOI: 10.1002/hep.25798
• 发表时间: 2012-10-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Tsuchiya, Hiroyuki;Ikeda, Yoshito;Shiota, Goshi
• 通讯作者: Shiota, Goshi

Hepatic iron overload induced by a high-fat, high-fructose dietoccurs prior to the onset of liversteatosis and insulin resistance via ahepcidin-independent mechanism inmice

高脂肪、高果糖饮食诱导的肝铁超负荷发生在小鼠肝脂肪变性和胰岛素抵抗之前，通过阿铁调素独立机制

• 发表时间: 2012
• 作者: H Tsuchiya;et al.
• 通讯作者: et al.

A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver.

视黄酸受体激动剂他米巴罗汀可抑制肝脏中铁的积累。

• DOI: 10.1002/oby.20013
• 发表时间: 2013
• 期刊: Obesity
• 影响因子: 6.9
• 作者: Teruko Hino-Arinaga;Tatsuya Ide;Ryoko Kuromatsu;Ichiro Miyajima I;Kei Ogata;Reiichiro Kuwahara;Akiko Hisamochi;Takuji Torimura;Michio Sata;Osamu Yoshikawa
• 通讯作者: Osamu Yoshikawa

レチノイドによるインスリン抵抗性改善作用に関わるSTAT3標的転写産物の網羅的探索

全面寻找类维生素A改善胰岛素抵抗作用中涉及的STAT3靶转录本

• 发表时间: 2012
• 作者: H Tsuchiya;et al.;山崎博;土谷博之
• 通讯作者: 土谷博之