血管周脂肪からの"血管内分泌"信号:インスリン抵抗性と血管疾患を結びつけるメカニズム
John S Yudkin1, Etto Eringa, Coen D A Stehouwer
1Diabetes and Cardiovascular Disease Academic Unit, Department of Medicine, Royal Free and University College Medical School, The Archway Campus, Holborn Union Building, 2-10 Highgate Hill, London N19 5LW, UK. j.yudkin@ucl.ac.uk
Lancet (London, England)
|May 25, 2005
まとめ
肥満は,脂肪の蓄積が腫瘍死滅因子アルファを放出するので,インスリンが血管に与える効果を損なう. これは血管収縮を引き起こし,インスリンが血管を拡張する能力を妨げます.
科学分野:
- 生理学 生理学とは
- エンドクリノロジー エンドクリノロジー
- 血管生物学 血管生物学
背景:
- 脂肪組織は,肝臓と筋肉のインスリンシグナル伝達に影響を与えるサイトカインを放出します.
- 肥満は,インスリンによる血管拡張の障害と関連しています.
- 動脈管の近くの局所的な脂肪堆積は,血管調節的な役割を果たす可能性があります.
研究 の 目的:
- 骨格筋の動脈細胞における近動脈脂肪の血管調節作用を調査する.
- インスリン媒介血管拡張と血管収縮のメカニズムを解明する.
- これらの血管反応に対する肥満の影響を調査する.
主な方法:
- ネズミのクレマスター筋から1次動脈の分離.
- インスリンがエンドセリン-1および酸化窒素 (NO) 経路に及ぼす影響の評価.
- 肥満ラットの動脈細胞におけるアディポチトカイン (腫瘍死滅因子アルファ) の関与の分析.
主要な成果:
- インスリンには二重の調節作用があります:エンドセリン-1媒介の血管収縮とNO媒介の血管拡張です.
- 肥満のネズミの動脈細胞は,インスリン刺激によるNO合成の障害を示し,無抵抗の血管収縮につながります.
- 周動脈脂肪からの腫瘍死滅因子アルファは,この血管拡張障害に関与しています.
結論:
- 肥満における周動脈脂肪貯蔵は,腫瘍死滅因子アルファを産生し,血管収縮を引き起こす.
- このサイトカインによる"血管内分泌"シグナル伝達は,インスリン媒介の毛細血管募集を阻害する.
- このメカニズムは,内臓脂肪,インスリン抵抗性,血管疾患を結びつける可能性があります.
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