Endoplasmic reticulum stress and the development of diabetes - A review
Endoplasmic reticulum stress and the development of diabetes - A review
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DOI：
10.2337/diabetes.51.2007.s455
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发表时间：
2002-12-01
期刊：
影响因子：
7.7
通讯作者：
Ron, D
中科院分区：
文献类型：
--
作者：
Harding, HP;Ron, D
胰岛素生物合成的早期步骤发生在内质网中。(ER)β-细胞具有高度发达和活跃的ER。所有细胞都调节其ER折叠和加工客户蛋白的能力，并且它们适应客户蛋白负载和折叠能力之间的不平衡（所谓的ER应激）。影响ER应激激活的胰腺ER激酶（PERK）及其下游效应子（翻译起始复合物真核起始因子2（eIF 2））的突变对胰岛细胞发育功能和存活具有深远影响。PERK突变与婴儿糖尿病的Wolcott-Rallison综合征和阻止eIF 2的α亚基被PERK磷酸化、阻断β细胞发育和损害胚胎发生的突变相关。我们将回顾这种和其他罕见形式的临床和实验性糖尿病，并考虑。ER应激在更常见的疾病形式的发展中的作用。
The early steps of insulin biosynthesis occur in the endoplasmic reticulum. (ER), and the beta-cell has a highly developed and active ER. All cells regulate the capacity of their ER to fold and process client proteins and they adapt to an imbalance between client protein load and folding capacity (so-called ER stress). Mutations affecting the ER stress-activated pancreatic ER kinase (PERK) and its downstream 1 effector, the translation initiation complex eukaryotic initiation factor 2 (eIF2), have a profound impact on islet cell development function, and survival. PERK mutations are associated with the Wolcott-Rallison syndrome of infantile diabetes and mutations that prevent the alpha-subunit of eIF2 from being phosphorylated by PERK, block beta-cell development, and impair gluconeogenesis. We will review this and other rare forms of clinical and experimental diabetes and consider the. role of ER stress in the development of more common forms of the disease.