インセプターは,β細胞におけるインスリンシグナル伝達を阻害し,血糖を制御する
Ansarullah1,2, Chirag Jain1,2, Fataneh Fathi Far1,3
1Institute of Diabetes and Regeneration Research, Helmholtz Center Munich, Neuherberg, Germany.
Nature
|January 28, 2021
まとめ
研究者達は 新しいタンパク質であるインセプタを発見し 臓のベータ細胞で インスリン信号を調節します インスリン受容体の活性を増強し,糖尿病治療の新たな治療標的となる可能性があります.
科学分野:
- 内分泌学
- 分子生物学
- 細胞生物学
背景:
- 胰腺ベータ細胞のインスリンおよびIGF1抵抗は糖尿病を引き起こす.
- ベータ細胞をインスリンに敏感にする治療は,ベータ細胞の衰えを防ぐことができます.
- ベータ細胞の信号伝達を理解することは 糖尿病の管理に不可欠です
研究 の 目的:
- 臓のβ細胞におけるインスリンとIGF1受容体シグナル伝達の新しい調節体を特定する.
- ベータ細胞の機能と発達におけるインスリン抑制受容体 (受容体) の役割を調査する.
- 糖尿病の治療目標として インセプターを探る
主な方法:
- インセプターノックアウト (Iir-/-) マウスの生成と分析.
- 臓組織と孤立した小島の分子と細胞の分析
- インスリン受容体 (INSR) とIGF1受容体 (IGF1R) の活性化とシグナリングの評価
- グルコース耐性とベータ細胞増殖のインビボ試験
- 受容体と受容体の相互作用を阻害するモノクローナル抗体の使用
主要な成果:
- インセプター・ノックアウトマウスは重度のインスリン血症,低血糖症,および胎内死亡率を示した.
- インセプターを失うと,INSR- IGF1Rの活性化,ベータ細胞の増殖,および質量が増加する.
- 誘導性β細胞特異的受容体ノックアウトは,成人マウスのグルコース耐性およびβ細胞増殖を改善する.
- インセプターはINSR- IGF1Rの無感化のためにクラトリン媒介の内細胞化を促進する.
- ベータ細胞におけるINSR- IGF1Rの活性化を維持する.
結論:
- 臓のベータ細胞を構成インスリンとIGF1シグナルから保護する重要なネガティブレギュレータとして作用します.
- インセプターはベータ細胞を過剰活性化から保護し,潜在的な障害を防ぐ.
- Inceptorはベータ細胞を敏感にし,糖尿病を治療するための治療法を開発するための有望な分子標的です.
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