Lin28/let-7軸は,グルコース代謝を調節する
Hao Zhu1, Ng Shyh-Chang, Ayellet V Segrè
1Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana Farber Cancer Institute, Boston, MA, USA.
Cell
|October 4, 2011
まとめ
Lin28/let-7経路は,予期せぬ方法で代謝を調節する. Lin28a/bの過剰発現はインスリン感受性と糖尿病抵抗性を改善し,Let-7の過剰発現はインスリン抵抗性を引き起こす.
科学分野:
- 分子生物学は分子生物学である.
- メタボリック・レギュレーション
- 遺伝学 遺伝学とは
背景:
- let-7マイクロRNAファミリーは,腫瘍遺伝子を調節することによって,腫瘍抑制剤として作用する.
- RNA結合タンパク質であるLin28a/bは,Let-7の生体生成を阻害し,がんを誘発する.
- Lin28/let-7経路の代謝における役割は,以前は知られていなかった.
研究 の 目的:
- 哺乳類のグルコース代謝におけるLin28/let-7経路の役割を調査する.
- リン28a/bとlet-7がインスリン感受性とグルコースホメオスタシスに与える影響を決定する.
主な方法:
- マウスでの過剰表現とノックアウトの研究.
- インスリン-PI3K-mTOR経路の構成要素の分析.
- グルコース耐性およびインスリン感受性の評価.
- 人間の遺伝子データのバイオ情報分析.
主要な成果:
- Lin28a/bがマウスで過剰発現すると,インスリン感受性と高脂肪食による糖尿病に対する耐性が生じる.
- 筋肉特有のLin28aの喪失またはlet-7の過剰発現は,インスリン抵抗性およびグルコース耐性の低下につながった.
- let-7はインスリン-PI3K-mTOR経路の重要な成分 (IGF1R,INSR,IRS2) を抑制しました.
- ラパミシン治療は,Lin28a媒介によるインスリン感受性を廃止しました.
- let-7のターゲットには,2型糖尿病と断食グルコースコントロールに関連したSNPを持つ遺伝子が含まれていた.
結論:
- Lin28/let-7経路は,グルコース代謝の重要な調節因子である.
- この経路は,インスリン-PI3K-mTORシグナリングカスケードを通じてインスリン感受性に影響します.
- let-7の標的における遺伝的変異は,ヒトの2型糖尿病と関連している.
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