Sharma Rohit B, Alonso Laura C
Diabetes Center of Excellence, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.
Curr Diab Rep. 2014 Jun;14(6):492. doi: 10.1007/s11892-014-0492-2.
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.
游离脂肪酸（FFAs）对β细胞存活和胰岛素分泌功能既有正面影响，也有负面影响，这取决于其浓度、作用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）产生的正向信号以及炎症介质和细胞因子等负向信号的调节。脂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（ER）应激以及可能的自噬。新的研究结果强化了一个古老的假说，即脂质也可能损害β细胞的代偿性增殖。临床观察继续支持脂质生物学在1型糖尿病（T1D）和2型糖尿病（T2D）的风险和进展中所起的作用。本综述总结了这一重要且快速发展领域的最新研究成果。
