通过CREB联合激活器CRTC2传感肝脏葡萄糖
Renaud Dentin1, Susan Hedrick, Jianxin Xie
1Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
概括
高水平的葡萄糖激活了胺生物合成途径 (HBP),导致蛋白质O-糖化. 这一由O-GlcNAcase调解的过程对于葡萄糖不耐受和糖尿病并发症至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 慢性高血糖是糖尿病并发症的关键驱动因素.
- 葡萄糖的升高激活了胺生物合成途径 (HBP).
- 在HBP激活时,通过O-glycosyl转移酶 (OGT) 促进蛋白质O-glycosylation.
研究的目的:
- 研究OGT介导的O-糖化在调节肝脏葡萄糖生成中的作用.
- 阐明OGT影响葡萄糖代谢的机制.
- 为了确定HBP在葡萄糖不耐症中的重要性.
主要方法:
- 研究了由OGT.通过调节的循环腺单酸盐反应元素结合蛋白2 (CRTC2) 的转换器的O-糖化.
- 研究了CRTC2 O-糖化酶的酸化依赖机制.
- 利用O-GlcNAcase降低O-糖基化CRTC2水平,并评估对葡萄糖生成的影响.
主要成果:
- 通过CRTC2.2的O-糖化,OGT会触发肝脏葡萄糖生成.
- CRTC2 O-糖化发生在依赖酸化的细胞质结合部位.
- 用O-GlcNAcase降低O-糖基化CRTC2抑制了葡萄糖诱导的葡萄糖生成.
结论:
- 在葡萄糖不耐症中,HBP起着至关重要的作用.
- 通过OGT介导的CRTC2的O-糖化是将高血糖与葡萄糖代谢受损联系起来的关键机制.
- 准OGT或O-GlcNA病例可能为糖尿病提供治疗策略.
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