School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
Annu Rev Biochem. 2012;81:767-93. doi: 10.1146/annurev-biochem-072909-095555. Epub 2012 Mar 23.
Given the functional importance of the endoplasmic reticulum (ER), an organelle that performs folding, modification, and trafficking of secretory and membrane proteins to the Golgi compartment, the maintenance of ER homeostasis in insulin-secreting β-cells is very important. When ER homeostasis is disrupted, the ER generates adaptive signaling pathways, called the unfolded protein response (UPR), to maintain homeostasis of this organelle. However, if homeostasis fails to be restored, the ER initiates death signaling pathways. New observations suggest that both chronic hyperglycemia and hyperlipidemia, known as important causative factors of type 2 diabetes (T2D), disrupt ER homeostasis to induce unresolvable UPR activation and β-cell death. This review examines how the UPR pathways, induced by high glucose and free fatty acids (FFAs), interact to disrupt ER function and cause β-cell dysfunction and death.
鉴于内质网（ER）在折叠、修饰和运输分泌蛋白和膜蛋白到高尔基体隔室方面的重要功能，维持胰岛素分泌β细胞中的内质网稳态非常重要。当内质网稳态被破坏时，内质网会产生适应性信号通路，称为未折叠蛋白反应（UPR），以维持这个细胞器的稳态。然而，如果稳态无法恢复，内质网会启动死亡信号通路。新的观察结果表明，高血糖和高血脂，即 2 型糖尿病（T2D）的重要致病因素，会破坏内质网稳态，导致不可解决的 UPR 激活和β细胞死亡。这篇综述探讨了高葡萄糖和游离脂肪酸（FFAs）诱导的 UPR 途径如何相互作用破坏内质网功能并导致β细胞功能障碍和死亡。
