構成的に活性なグルカゴン受容体は,鳥の高血糖を誘導する

Chang Zhang¹, Xiangying Xiang¹, Jian Liu²

¹Department of Respiratory and Critical Care Medicine, Center for High Altitude Medicine, Institutes for Systems Genetics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Nature

|March 3, 2025

まとめ

鳥類のグルカゴン受容体 (GCGR) の高い発現は,種ごとに血糖と代謝率を増加させる. この発見は鳥の飛行の進化を説明し代謝の調節に関する洞察を与えます

科学分野:

内分泌学
代謝の調節
進化生物学

背景:

主に保存されたグルカゴン受容体 (GCGR) 家族によって調節される.
鳥類は他の脊椎動物よりも血糖値が高く,その基礎となる規制メカニズムは十分に理解されていません.

研究の目的:

鳥類のグルカゴン受容体 (GCGR) 発現とその関連信号が血糖調節における役割を調査する.
鳥類の代謝適応,特に飛行の文脈におけるGCGR活動の進化的影響を探求する.

主な方法:

鳥のGCGRの肝臓発現とドメインの相互作用を通してその構成Gsのシグナリング活性を調べた.
様々な種 (魚,爬虫類,鳥,哺乳類) において,肝細胞における構成的に活性なGCGRの影響を評価するために,in vivo実験を実施した.
GCGR mRNA発現と体重に影響を与える特定の点変異を鶏で特定し,ヒトのGCGR変異をマウスで過剰発現した.

主要な成果:

肝細胞における構成的に活性なGCGRは,血糖値の上昇,肝脂質の利用率の増加,および試験されたすべての脊椎動物群におけるより高い代謝率をもたらした.
GCGR遺伝子の近くの鶏の突然変異は,減少したGCGR mRNAと体重増加と相関する.
マウスの体内では,適度に活性化しているヒトGCGRの過剰発現により,血糖値が上昇し,体重が低下した.

結論:

GCGRの高肝発現と構成活動は,高血糖と代謝率の主要な要因である.
これらのGCGRの特徴は鳥類の祖先の飛行の進化に極めて重要だったのかもしれません
GCGR活動は,脊椎動物の代謝率と体重に影響を与え,エネルギーホメオスタシスの保存された役割を強調します.

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