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インスリン/IGF-1はPERIOD合成を駆動し,食事時間とともに循環リズムを誘導する
Priya Crosby1, Ryan Hamnett1, Marrit Putker2
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Cell
|April 30, 2019
まとめ
栄養ホルモンであるインスリンとIGF-1は,PERIODタンパク質を誘発することで,哺乳類の昼夜時計をリセットします. インスリン信号のタイミングが間違えば 日常リズムとクロック遺伝子発現が乱され 生理学に影響します
科学分野:
- クロノバイオロジー
- 内分泌学
- 分子生物学
背景:
- 哺乳類の昼間時計は 食事や光といった 環境のシグナルに合わせて 調整されます
- 昼夜リズムが乱れ,しばしば誤った食事 (シフト労働など) が原因で,2型糖尿病のような代謝疾患に結びついている.
研究 の 目的:
- 生理時計のリセットにおける 栄養調節ホルモンの役割を調べる
- インスリンとIGF-1が昼夜組織に影響を与える分子メカニズムを解明する.
主な方法:
- 哺乳類のモデルを用いた in vivo および in vitro 実験
- PERIODタンパク質誘導とインスリン/IGF-1シグナル伝達との関係の分析
- 行動と時計の遺伝子発現のサーカディアン組織の評価
主要な成果:
- インスリンとIGF-1は,PERIODタンパク質を誘導することで,昼間の時計をリセットすることが示されました.
- 誤ったインスリン信号は 行動リズムやマウスの時計遺伝子発現を 妨害しました
- インスリン/IGF-1受容体のシグナル伝達,mTORの活性化,およびマイクロRNAのダウンレギュレーションは,このプロセスの重要な構成要素として特定されました.
結論:
- インスリンとIGF-1は 細胞の時計に 栄養を与える重要な信号として作用します
- これらのホルモンは,昼夜組織と生理学的ホメオスタシスの維持に不可欠です.
- この経路を理解することで,日中活動障害に関連した代謝疾患の発達に関する洞察が得られます.
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