伊诺西托-1,4,5-三酸盐受体调节肝脏葡萄糖生成在禁食和糖尿病
Yiguo Wang1, Gang Li, Jason Goode
1Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature
|April 13, 2012
概括
葡萄糖素通过激活信号传递来刺激肝脏葡萄糖的产生,该信号传递去化CRTC2. 这一途径在糖尿病中失调,但向它可以改善葡萄糖水平.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 激素信号传递 激素信号传递
背景情况:
- 葡萄糖激素通过循环AMP (cAMP) 途径促进肝脏葡萄糖的产生,涉及CRTC2脱.
- 将荷尔蒙线索与通过Ser/Thr酸酶的CRTC2脱化联系在一起的精确机制尚未完全理解.
研究的目的:
- 阐明细胞内储存和氨酸在肝细胞中葡萄糖介导的CRTC2脱化中的作用.
- 研究胰岛素信号传递对这种途径的调节及其对糖尿病的影响.
主要方法:
- 用小鼠肝细胞进行的研究,以检查葡萄糖素对调动和CRTC2酸化的影响.
- 研究了异醇-1,4,5-三酸盐受体 (InsP(3) Rs),CRTC2和氨酸尿素之间的相互作用.
- 评估了胰岛素信号和糖尿病对InsP(3) R活性和葡萄糖生成的影响.
主要成果:
- 葡萄糖刺激肝细胞中的CRTC2脱化,通过调动细胞内和激活尿.
- 这一过程涉及PCA介导的CRTC2-关联InsP(3) Rs的酸化,增强葡萄糖原性基因表达.
- 胰岛素信号失活InsP(3) Rs,降低在食期间的CRTC2活性; InsP(3) R活性在糖尿病中升高.
结论:
- 葡萄糖利用一个cAMP和信号轴,涉及InsP(3)Rs和氨酸,以调节肝脏的葡萄糖生产.
- 失调的InsP(3) R活性有助于糖尿病中葡萄糖生成的上调.
- 针对肝脏的InsP(3)Rs和氨酸,为胰岛素抵抗和糖尿病提供了潜在的治疗策略.
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