Cytoprotection of Beta Cells Through Modulation of Ire1Alpha Function

项目总结/摘要 许多最近的研究将2型糖尿病（T2 D）的发展与内质网 内质网（ER）应激，当蛋白质折叠需要时发生的一种情况 压倒了分泌途径中的蛋白质折叠能力。值得注意的是， 证据表明，ER应激有助于减少葡萄糖反应性胰岛素分泌， 细胞凋亡，以及一般外周胰岛素抵抗，这些都是T2 D的标志。 内质网应激触发未折叠蛋白反应（UPR）途径，减缓翻译 并转录调节增强内质网蛋白折叠能力的基因。如果 如果体内平衡没有通过这些输出恢复，UPR反而触发细胞凋亡。我们 假设普遍定期审议关键组成部分，作为一个在 稳态和凋亡输出，最终控制细胞命运。我们的项目目标是 使用介入方法在分子水平上研究这些开关。

Project Summary/Abstract Numerous recent studies link development of type 2 diabetes (T2D) to endoplasmic reticulum (ER) stress, a condition that occurs whenever protein-folding requirements overwhelm protein-folding capacity in the secretory pathway. Notably, there is mounting evidence that ER stress contributes to diminished glucose-responsive insulin secretion in ¿- cells, to¿-cell apoptosis, and to generalperipheral insulin resistance, all hallmarks of T2D. ER stress triggers the unfolded protein response (UPR) pathway, which slows translation and transcriptionallyupregulates genes that enhance ER protein-folding capabilities. If homeostasis is not restored through these outputs, the UPR triggers apoptosis instead. We hypothesize that key component of the UPR, act as a toggling switches between homeostatic and apoptotic outputs, ultimately controlling ¿-cell fate. Our project goal is to study these switches at the molecular level using interventional approaches.