アンジオテンシン1型受容体阻害剤は,ペロキソーム増殖器活性化受容体-ガンマ活性化を誘発する
Michael Schupp1, Jürgen Janke, Ronald Clasen
1Center for Cardiovascular Research, Institut für Pharmakologie und Toxikologie, Campus Charité-Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Circulation
|May 1, 2004
まとめ
特定のアニオテンシン1型受容体阻害剤 (ARB) は,ペロキソーム増殖器活性化受容体ガンマ (PPARgamma) 活性化を高め,アディポサイトの分化を促進します. これは,ARBのインスリン感受性および抗糖尿病効果のための潜在的なメカニズムを提供します.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
- 薬理学 薬理学とは
背景:
- アンジオテンシン1型受容体阻害剤 (ARB) は,未知のメカニズムを通じて2型糖尿病の発生率を減らすことが知られている.
- ペロキシソーム増殖器活性化受容体ガンマ (PPARgamma) は,インスリン感受性およびグルコース代謝の重要な調節体です.
研究 の 目的:
- ARBがPPARガンマ機能をどのように調節するかを調査する.
- ARBsの抗糖尿病効果の基礎となる分子メカニズムを探求する.
主な方法:
- 定量的リアルタイムPCRで,アディポゲンマーカー遺伝子アディポスタンパク質2 (aP2) のmRNA発現を測定する.
- トランスクリプション・レポーターは,PPARガマのトランスクリプション活動を評価するためのアッセイである.
- AT1R欠乏細胞モデル (PC12W) を用いた実験.
主要な成果:
- イルベサルタンとテルミサルタン (10ミクロモール/L) は,PPARガンマ依存の3T3-L1アディポサイト分化とaP2mRNA発現を著しく強化した.
- テルミサルタンは,薬理学的に重要な濃度でより強力なaP2誘導を示した.
- イルベサルタンとテルミサルタンは,AT1R欠乏細胞モデルで示されているように,AT1R阻害とは無関係にPPARgamma活性を引き起こす.
結論:
- 特定のARBはPPARgammaを活性化し,脂肪細胞の分化を促進する.
- このPPARgammaの活性化は,特定のARBの新しいプレオトロプ的作用を表しています.
- このメカニズムは,一部のARBで観察されたインスリン感受性および抗糖尿病効果を説明する可能性がある.
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