The molecular mechanism of insul in resistance induced by overnutrition

胰岛素抗营养过剩的分子机制

• 批准号: 20890279
• 负责人: TSUTSUMI Rie
• 金额: $ 2.11万
• 依托单位: Mukogawa Women's University Junior College Division
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (Start-up)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20890279/
• 关键词: mTOR; 栄養; Rheb; 肝臓; インスリン抵抗性; たんぱく質合成; トランスロケーション; Vps34; アミノ酸

Liver has the critical role in amino acids uptake and protein synthesis from amino acid as well as some insulin actions. p70 rebosomal protein kinase 1 (S6K1) is the key regulator of translation and its over activation induces insulin resistance by negative feedback to IRS1. However, its regulation of S6K1 has not be clear yet. In this study, we hypothesized that Vps34 and Rheb play a role of mTOR-S6K1 signaling as a nutrient sensor and GTP-bound Rheb induces endosome trafficking to activate mTOR. There results indicate Vps34 and Rheb, which is activated by nutritional uptake, regulate S6K1 and translocation of Rheb is critical for activation of mTOR-S6K1 signaling.

肝脏在氨基酸的摄取和蛋白质合成以及胰岛素的作用中起着关键的作用。P70重组蛋白激酶1(S6K1)是翻译的关键调节因子，其过度激活通过对IRS1的负反馈而诱导胰岛素抵抗。然而，它对S6K1的调控还不清楚。在本研究中，我们假设Vps34和Rheb在mTOR-S6K1信号通路中起营养感受器的作用，并且与GTP结合的Rheb诱导内体转运来激活mTOR。这些结果表明，Vps34和Rheb被营养摄取激活，调节S6K1，Rheb的易位是激活mTOR-S6K1信号的关键。

项目成果

pulsality, the pituitary response and reproductive dysfunction.

脉动、垂体反应和生殖功能障碍。

• 发表时间: 2009
• 期刊: Endocrine Journal 56(6)
• 作者: RIE TSUTSUMI;NICHOLAS J.C.;WEBSTER;GnRH
• 通讯作者: GnRH

GnRH pulsatility, the pituitary response and reproductive dysfunction.

• DOI: 10.1507/endocrj.k09e-185
• 发表时间: 2009
• 期刊: Endocrine journal
• 影响因子: 2
• 作者: Tsutsumi R;Webster NJ
• 通讯作者: Webster NJ