インスリンは,コアクティベーターTORC2を阻害することによって,グルコネオゲネシスを調節する
Renaud Dentin1, Yi Liu, Seung-Hoi Koo
1Peptide Biology Laboratories, Salk Institute For Biological Studies, La Jolla, California 92037, USA.
Nature
|September 7, 2007
まとめ
インスリンは,グルコン生成の重要なタンパク質であるTORC2を分解することによって,グルコースの産生を制御する. この経路は,この経路です.
科学分野:
- メタボリズムは
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
背景:
- インスリンシグナリングは,AKTとFOXO1のリン酸化経由で肝臓のグルコース生成を抑制する.
- FOXO1とTORC2 (CRTC2) は,断食状態でグルコネオゲン遺伝子の発現を促進するために協力します.
- グルカゴンのシグナル伝達は,TORC2の核転位と,CREB媒介によるグルコネオゲネシスの刺激につながる.
研究 の 目的:
- 再給餌中にインスリンがグルコネオゲン遺伝子発現を抑制するメカニズムを解明する.
- インスリンによるTORC2.2の調節におけるSIK2とCOP1の役割を調査する.
主な方法:
- 研究はマウスで実施された.
- 分子生物学の技術を用いてタンパク質のリン酸化,分解,および局所化を研究した.
- ユビキチネーションアッセイとプロテアソーム分解研究を利用した.
主要な成果:
- インスリンは,再給餌中にTORC2のリン酸化とユビキチン依存の分解を促進します.
- インスリンがSIK2を誘導し,SIK2はTORC2.2の細胞質転移をリン酸化し,促進する.
- COP1は,TORC2のユビキチン化と26Sプロテアソームによる分解を媒介する.
結論:
- インスリンは,SIK2-COP1経路を通じた分解のためのTORC2をターゲットにすることで,グルコネオゲネシスを抑制します.
- 糖尿病におけるTORC2濃度の上昇によって特徴づけられるこの経路の調節障害は,グルコースホメオスタシスの障害に寄与する.
- このメカニズムは,TORC2の調節が血糖のバランスを維持する上で重要な役割を果たしていることを強調しています.
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