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一个禁食诱导开关通过激活剂/协同激活剂交换调节葡萄糖生成
Yi Liu1, Renaud Dentin, Danica Chen
1The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, California 92037, USA.
Nature
|October 14, 2008
概括
禁食通过在CRTC2和FOXO1.1之间切换来调节能量平衡. 赛尔图因1 (SIRT1) deacetylates CRTC2,促进FOXO1活动,并在长时间禁食期间维持葡萄糖平衡.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子内分泌学分子内分泌学
- 营养物质感应 营养物质感应
背景情况:
- 禁食通过葡萄糖激发肝脏葡萄糖生成,涉及CRTC2和FOXO1.
- 胰岛素信号减少,在禁食期间增加葡萄糖生成.
- 在晚期禁食期间,体提供补偿燃料.
研究的目的:
- 研究p300和SIRT1在保持禁食期间的能量平衡中的作用.
- 阐明CRTC2和FOXO1.1的顺序诱导和调节.
主要方法:
- 使用了具有肝脏特异性Sirt1基因淘汰的小鼠模型.
- 管理的SIRT1抗剂和激动剂.
- 评估了蛋白质的脱,乙和无处不在.
- 测量了葡萄糖基因表达和葡萄糖输出.
主要成果:
- 禁食诱导了涉及p300和SIRT1的开关,以调节CRTC2和FOXO1.
- p300 乙化并激活CRTC2;SIRT1 脱乙化并降低CRTC2.
- SIRT1的激活相互激活FOXO1和PGC-1alpha.
- 破坏SIRT1会增加CRTC2活动和葡萄糖输出.
结论:
- 一个快速诱导的p300和SIRT1的开关保持能量平衡.
- 这种开关对CRTC2和FOXO1的顺序激活对于葡萄糖平衡至关重要.
- 在禁食期间,SIRT1在调节葡萄糖生成中发挥着关键作用.
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