臓β細胞増強剤は,インスリン分泌を制御する遺伝子のリズム転写を調節する

Mark Perelis¹, Biliana Marcheva¹, Kathryn Moynihan Ramsey¹

¹Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Science (New York, N.Y.)

|November 7, 2015

まとめ

臓細胞におけるBMAL1遺伝子の破壊はインスリン分泌を阻害し,グルコース不耐性を引き起こし,生体時計が代謝の健康と糖尿病における役割を強調する.

科学分野:

内分泌学
分子生物学
クロノバイオロジー

背景:

CLOCKとBMAL1によって調節される哺乳類の昼夜リズムは,行動と代謝の調整に不可欠です.
2型糖尿病などの代謝障害に繋がっています
臓のベータ細胞機能における細胞自律時計の役割は,まだ完全に解明されていない.

研究の目的:

細胞自律的な昼間の時計が臓のベータ細胞機能に与える影響を調べる
BMAL1の障害が生涯を通じて,成人期にわたってインスリン分泌とグルコース代謝にどのように影響するかを調べる.

主な方法:

BMAL1発現が保たれたか,破損したマウスの臓小島を研究した.
インスリン分泌パターンと分泌機構に関連する遺伝子発現を分析した.
CLOCK/BMAL1とPDX1のコロカライゼーションを研究した.

主要な成果:

インスリン分泌とインスリン放出を調節する遺伝子の同期した振動が観察されました.
肝臓の代謝ネットワークとは異なり,CLOCK/BMAL1がPDX1とコロカライズされていることが判明した.
成人マウスのベータ細胞クロック剥離は重度のグルコース不耐性を引き起こすことが示された.

結論:

細胞型特異な増強剤は,生涯にわたる周周周代謝の昼夜制御を媒介する.
この発見は,糖尿病における昼夜不調の潜在的メカニズムを示唆している.
ベータ細胞の昼間時計の整合性を維持することは,代謝の恒常性のために不可欠です.

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