エンドプラズマ網膜のストレスは,肥満,インスリン作用,および2型糖尿病と関連しています
Umut Ozcan1, Qiong Cao, Erkan Yilmaz
1Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|October 16, 2004
まとめ
肥満に起因するエンドプラズマ網膜 (ER) のストレスは,c-Jun N-ターミナルキナーゼ (JNK) とインスリン受容体基板-1 (IRS-1) のリン酸化を活性化することによってインスリンシグナル伝達を抑制し,2型糖尿病に寄与します.
科学分野:
- メタボリック疾患は,
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 肥満は2型糖尿病の主要な危険因子です.
- 肥満とインスリン抵抗性を結びつける分子機構は完全に理解されていません.
研究 の 目的:
- 肥満に関連するインスリン抵抗性におけるエンドプラズマ網膜 (ER) ストレスの役割を調査する.
- ERストレス誘発型インスリンシグナルシグナル抑制に関与する分子経路を解明する.
主な方法:
- 肥満とERストレスを研究するために,細胞培養とマウスモデルを使用しました.
- c-Jun N-ターミナルキナーゼ (JNK) の活性化とインスリン受容体基板-1 (IRS-1) のリン酸化を調べました.
- ERストレスとインスリン抵抗性におけるX-box-binding protein-1 (XBP-1) の機能を調査した.
主要な成果:
- 肥満は,エンドプラズマ網膜 (ER) のストレスを誘発することが示されました.
- ERのストレスは,JNK過活性化とIRS-1セリンリン酸化によるインスリン受容体のシグナル伝達抑制につながった.
- X-box-binding protein-1 (XBP-1) が欠けていたマウスは,インスリン抵抗性を示した.
結論:
- エンドプラズマ網膜 (ER) のストレスは,外周インスリン抵抗性や2型糖尿病の根底にある重要な分子機構です.
- ERストレス経路をターゲットにすることは,肥満と2型糖尿病の潜在的な治療戦略です.
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