Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well?
Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well?
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DOI：
10.1007/s11892-014-0492-2
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发表时间：
2014-06
影响因子：
4.2
通讯作者：
Alonso LC
中科院分区：
文献类型：
--
作者：
Sharma RB;Alonso LC
游离脂肪酸（FFAs）对β细胞存活和胰岛素分泌功能有积极和消极的影响，这取决于其浓度、持续时间和葡萄糖丰度。脂质信号不仅通过代谢途径介导，还通过细胞表面和细胞核受体介导。毒性受到循环因子如激素、生长因子和肠促胰岛素产生的积极信号以及炎症介质和细胞因子等消极信号的调节。脂肪毒性的细胞内机制包括代谢干扰和细胞应激反应，如氧化应激、内质网应激和可能的自噬。新的发现加强了一个古老的假设，即脂质也可能损害代偿性β细胞增殖。临床观察继续支持脂质生物学在1型（T1D）和2型糖尿病（T2D）的风险和进展中的作用。本文综述了这一重要而迅速发展的领域的最新工作。
Free fatty acids (FFAs) exert both positive and negative effects on beta cell survival and insulin secretory function, depending on concentration, duration, and glucose abundance. Lipid signals are mediated not only through metabolic pathways, but also through cell surface and nuclear receptors. Toxicity is modulated by positive signals arising from circulating factors such as hormones, growth factors and incretins, as well as negative signals such as inflammatory mediators and cytokines. Intracellular mechanisms of lipotoxicity include metabolic interference and cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and possibly autophagy. New findings strengthen an old hypothesis that lipids may also impair compensatory beta cell proliferation. Clinical observations continue to support a role for lipid biology in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This review summarizes recent work in this important, rapidly evolving field.