脂肪組織にある新しいChREBP同型は,全身のグルコース代謝を調節する
Mark A Herman1, Odile D Peroni, Jorge Villoria
1Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Nature
|April 3, 2012
まとめ
脂肪組織 GLUT4 (グルコーストランスポーター) は,ChREBP (脂肪合成における重要なタンパク質) を調節する. 新しいChREBP同型 (ChREBP-β) は,インスリン感受性を予測し,糖尿病治療の潜在的な標的を提供している.
科学分野:
- メタボリズムは
- 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.
背景:
- 世界的に肥満と2型糖尿病の割合が上昇していることは,健康に重大なリスクをもたらしています.
- 周辺組織,特に脂肪組織におけるインスリン作用の低下は,糖尿病の病原性における重要な要因である.
- 脂肪組織グルコーストランスポーターGLUT4 (SLC2A4) は,インスリン刺激によるグルコース吸収と全身インスリン感受性において重要な役割を果たします.
研究 の 目的:
- 脂肪組織GLUT4と転写調節器ChREBP (MLXIPL) の間の調節関係を調査する.
- 脂肪酸合成と全身インスリン感受性における脂肪系ChREBPの役割を明らかにする.
- ChREBPのグルコース調節の新しいメカニズムを特定し,糖尿病の治療標的としての可能性を調査する.
主な方法:
- 脂肪組織におけるGLUT4発現とそのChREBPへの影響の分析.
- 新型同型 (ChREBP-β) を含むChREBP同型の転写制御を調査する.
- ヒトの脂肪組織におけるCHREBP-β発現と相関する,全身インスリン感受性.
主要な成果:
- 脂肪組織GLUT4は,炭水化物反応性元素結合タンパク質 (ChREBP) の発現を調節することが判明しました.
- Adipose ChREBPは,脂肪組織の脂肪酸合成と全体的な全身インスリン感受性に大きな影響を与えます.
- グルコースがChREBP-αを活性化する新しいメカニズムが特定され,代替プロモーターから強力なChREBP-βイソフォームの発現を誘導しました.
結論:
- 脂肪組織 GLUT4 と ChREBP は,糖尿病に関連する代謝過程の相互接続されたレギュレータです.
- 新たに特定されたChREBP-β同型は,グルコースによって調節され,脂肪組織で発現され,インスリン感受性の強力な予測因子です.
- ChREBP-βは,インスリン感受性の改善と2型糖尿病の治療のための有望な治療標的を表しています.
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