模仿禁食的饮食促进了NGN3驱动的β细胞再生以逆转糖尿病
Chia-Wei Cheng1, Valentina Villani2, Roberta Buono3
1Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA; Koch Institute at MIT, 500 Main Street, Cambridge, MA 02139, USA.
Cell
|February 25, 2017
概括
一种模仿禁食的饮食可以在小鼠和人类胰腺细胞中再生胰岛素. 这种饮食干预可以通过恢复葡萄糖平衡和胰岛素分泌来逆转1型和2型糖尿病.
科学领域:
- 代谢疾病
- 复原医学
- 内分泌学
背景情况:
- 干细胞疗法提供了器官再生的潜力, 但面临着组织去除和启动再生计划的挑战.
- 糖尿病包括1型和2型,其特征是胰岛素的产生受损和葡萄糖的失调.
研究的目的:
- 研究仿制禁食饮食 (FMD) 诱导胰腺细胞重编程和再生的潜力.
- 在糖尿病和人类胰腺小岛的临床前模型中评估口疾病在恢复胰岛素分泌和葡萄糖平衡方面的疗效.
主要方法:
- 对1型和2型糖尿病的小鼠模型进行了为期4天的禁食模仿饮食 (FMD).
- 在小鼠和人类胰腺小岛中进行了基因表达分析 (Sox17,Pdx-1,Ngn3,Sox2).
- 评估了胰岛素的产生和葡萄糖的稳定性.
- 检查了口病与IGF-1治疗以及抑制PKA和mTOR信号通路的作用.
主要成果:
- 在小鼠中诱导Sox17,Pdx-1和Ngn3的逐步表达,促进产生胰岛素的β细胞.
- 在1型和2型糖尿病小鼠模型中,口疾病循环恢复了胰岛素分泌和葡萄糖平衡.
- 在人类1型糖尿病群岛中,禁食降低了PKA和mTOR活性,增加了Sox2,Ngn3表达和胰岛素的产生,这些效应被PKA/mTOR抑制模仿并被IGF-1逆转.
结论:
- 模仿禁食的饮食可以促进胰腺细胞的重新编程以恢复胰岛素的产生.
- 在小鼠模型中,口病具有逆转1型和2型糖尿病的潜力.
- 通过增强内源性再生能力,口病可能为糖尿病提供一种新的治疗策略.
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