腫瘍死滅因子-αは,ヒトにおけるグルコース吸収と内皮に依存した血管拡張に対するインスリン刺激効果を阻害する
Christian Rask-Madsen1, Helena Domínguez, Nikolaj Ihlemann
1Joslin Diabetes Center, Section on Vascular Cell Biology and Complications, One Joslin Place, Room 4504, Boston, Mass 02215, USA. christian.rask-madsen@joslin.harvard.edu
Circulation
|October 8, 2003
まとめ
腫瘍死滅因子アルファ (TNF-alpha) は,ヒトにおけるインスリン刺激によるグルコース吸収と内皮機能を著しく低下させる. これは,TNF-αが筋肉と血管組織の両方のインスリン抵抗性に貢献することを示唆しています.
科学分野:
- 人間の生理学 人間の生理学
- メタボリック障害 メタボリック障害
- 炎症 炎症 炎症 炎症 炎症
背景:
- 炎症的メカニズムは,インスリン抵抗性や動脈硬化に関与しています.
- 腫瘍死滅因子アルファ (TNF-alpha) は,炎症を誘発する重要なサイトカインである.
研究 の 目的:
- TNF-αがヒトにおけるインスリン刺激によるグルコース吸収を阻害するかどうかを調査する.
- インスリン刺激による内皮機能に対するTNF-αの効果を検証する.
主な方法:
- 健康な男性ボランティアは,腕動脈注入を受けた.
- アセチルコリン (ACh) とナトリウムニトロプルシド (SNP) との投与量反応研究が行われました.
- インスリンおよび/またはTNF-αを共注入して,グルコースの吸収と血流に対する影響を評価した.
主要な成果:
- インスリン刺激による前腕のグルコース吸収は220%増加したが,TNF-alpha.comによって完全に抑制された.
- TNF-αは,特にインスリン注入中に,ACH誘発前腕の血流を著しく抑制しました.
- ACh反応に対するTNF-αの阻害は,窒素酸化物 (NO) 産出の減少によって媒介された可能性が高い.
結論:
- TNF-αは,ヒトの筋肉におけるインスリン抵抗性の発生に作用する.
- TNF-αは血管機能不全に寄与し,動脈硬化症の発達に作用することを示唆しています.
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