ハベヌラ TCF7L2は,ニコチン依存症と糖尿病を関連付けています
Alexander Duncan1,2, Mary P Heyer1, Masago Ishikawa1
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nature
|October 18, 2019
まとめ
糖尿病に関連した遺伝子Tcf7l2が脳内にある
科学分野:
- 神経科学
- 遺伝学
- 内分泌学
背景:
- 喫煙は糖尿病の発生率を高めますが そのメカニズムは不明です
- Tcf7l2遺伝子は糖尿病と関連しています.
- このリンクにおける脳の中央部 (mHb) の役割は不明である.
研究 の 目的:
- ニコチンがグルコース代謝に及ぼす影響について,中央ヘブンヌラ (mHb) のTcf7l2の役割を調査する.
- ニコチン消費と Tcf7l2 と 糖尿病のような症状を結びつける神経経路を探る
主な方法:
- ネズミのmHbにおけるTcf7l2表現を調べた.
- ニコチン摂取を評価するためにmHbのTCF7L2信号を抑制した.
- 野生型とTcf7l2変異のラットにおけるニコチン曝露後の血糖,インスリン,およびグルカゴン値の測定
- mHbから臓までの 神経接続をマッピングするために ウイルスを追跡した.
主要な成果:
- Tcf7l2はmHbで高く表現され,ニコチンアセチルコリン受容体を調節する.
- mHbのTCF7L2を阻害すると,ニコチン摂取が増加します.
- ニコチンはTCF7L2依存のmHb刺激によって血糖を上昇させる.
- mHbから臓への神経経路が特定されました.
- ニコチンに曝された野生型のネズミは,Tcf7l2変異のネズミとは異なり,グルコースホメオスタシスの変化を示した.
結論:
- mHbのTcf7l2は,ニコチンの刺激作用をハベヌラ-臓軸に媒介する.
- この軸はニコチン依存症と 糖尿病を誘発する行動を関連付けています
- Tcf7l2はニコチン使用と糖尿病発症の神経生物学的な関連における重要な調節因子です.
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