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mTORC1 Signaling: A Double-Edged Sword in Diabetic beta Cells

机译:MTORC1信号:糖尿病β细胞中的双刃剑

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摘要

The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of metabolic and nutrient cues that integrates environmental inputs into downstream signaling pathways to control cellular metabolism, growth, and survival. While numerous in vitro and in vivo studies reported the positive functions of mTORC1 in the regulation of beta cell survival and proliferation under physiological conditions, more recent work demonstrates the opposite in the long term; this is exemplified by the constitutive inappropriate hyper-activation of mTORC1 in diabetic islets or beta cells under conditions of increased beta cell stress and metabolic demands. These recent findings uncover mTORC1's importance as an emerging significant player in the development and progression of beta cell failure in type 2 diabetes and suggest that mTORC1 may act as a "double edge sword" in the regulation of beta cell mass and function in response to metabolic stress such as nutrient overload and insulin resistance.
机译:雷帕霉素复合物1(MTORC1)的机械靶标是代谢和营养提示的中央调节因子,其将环境投入集成到下游信号传导途径中,以控制细胞代谢,生长和生存。虽然许多体外和体内研究报告了MTORC1在生理条件下调节β细胞存活和增殖中的MTORC1的阳性功能,但最近的工作在长期内表现出相反的工作;这是在增加的β细胞应激和代谢要求的条件下的糖尿病患者或β细胞中MTORC1的组成型不恰当的超激活。这些最近的发现发现MTORC1在2型糖尿病中的开发和进展中的出现和进展的重要性,并表明MTORC1可以作为“双刃剑”在β细胞质量调节中起作用,响应于代谢的功能压力如营养过载和胰岛素抵抗。

著录项

  • 来源
    《Cell metabolism》 |2018年第2期|共18页
  • 作者单位

    Univ Bremen Ctr Biomol Interact Bremen D-28359 Bremen Germany;

    Univ Bremen Ctr Biomol Interact Bremen D-28359 Bremen Germany;

    Kobe Univ Div Diabet &

    Endocrinol Dept Internal Med Grad Sch Med Kobe Hyogo 6500017 Japan;

    Hadassah Hebrew Univ Med Ctr Dept Med Endocrinol &

    Metab Serv IL-91120 Jerusalem Israel;

    Univ Bremen Ctr Biomol Interact Bremen D-28359 Bremen Germany;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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