Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Autophagy. 2012 Feb 1;8(2):158-64. doi: 10.4161/auto.8.2.18807.
In pancreatic β-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the β-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to an imbalance in protein homeostasis and ER stress, which has been recognized as an important mechanism for type 2 diabetes. Macroautophagy (hereafter referred to as autophagy) is activated as a novel signaling pathway in response to ER stress. In this review, we outline the mechanism of ER stress-mediated β-cell death and focus on the role of autophagy in ameliorating ER stress. The development of drugs to take advantage of the potential protective effect of autophagy in ER stress, such as glucagon like peptide-1, will be a promising avenue of investigation.
在胰腺 β 细胞中，内质网（ER）是胰岛素生物合成的关键部位，因为这里是分泌蛋白的蛋白质折叠机制所在的地方。β 细胞 ER 功能的扰动，如由高水平游离脂肪酸和胰岛素抵抗引起的那些，可能导致蛋白质动态平衡和内质网应激的失衡，这已被认为是 2 型糖尿病的重要机制。自噬（以下简称自噬）作为一种新的信号通路被激活，以响应内质网应激。在这篇综述中，我们概述了内质网应激介导的β细胞死亡的机制，并重点介绍了自噬在减轻内质网应激中的作用。开发利用自噬在内质网应激中的潜在保护作用的药物，如胰高血糖素样肽-1，将是一个有前途的研究方向。
