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Cytoprotection of Beta Cells Through Modulation of Ire1Alpha Function

通过调节 Ire1Alpha 功能对 Beta 细胞进行细胞保护

基本信息

批准号：
8274825
负责人：
Feroz R Papa
金额：
$ 32.94万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8274825
关键词：
Adenoviruses Affect American Apoptosis Apoptotic Beta Cell Biogenesis Cell Death Cell Survival Cell physiology Cells Cessation of life Co-Immunoprecipitations Cytoprotection Data Development Disease Drug Delivery Systems Endoplasmic Reticulum Event Functional disorder Genes Glucose Goals Healthcare Homeostasis Individual Insulin Insulin Resistance Integral Membrane Protein Islet Cell Islets of Langerhans Life Link Messenger RNA Microarray Analysis Molecular Molecular Chaperones Monitor Non-Insulin-Dependent Diabetes Mellitus Organism Output Oxidoreductase Pathway interactions Pharmaceutical Preparations Phosphotransferases Physiological Physiology Play Positioning Attribute Process Production Productivity Proinsulin Proteins RNA Splicing Recombinants Reporter Resistance Ribonucleases Role Signal Pathway Signal Transduction Stress System Testing Translations Work abstracting arm assault base cDNA Arrays cost diabetic endoplasmic reticulum stress insight insulin secretion islet islet amyloid polypeptide programs protein folding research study response secretory protein tool transcription factor

项目摘要

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.

项目摘要/摘要最近的许多研究将2型糖尿病(T2D)的发生与内质网联系起来网状(ER)应激，当蛋白质折叠需要时发生的一种情况在分泌途径中压倒蛋白质折叠能力。值得注意的是，有越来越多的有证据表明，内质网应激导致葡萄糖反应性胰岛素分泌减少。细胞，细胞凋亡，以及外周胰岛素抵抗，这些都是T2D的特征。内质网应激触发未折叠蛋白反应(UPR)途径，从而减缓翻译转录上上调增强ER蛋白折叠能力的基因。如果动态平衡不是通过这些输出来恢复的，相反，UPR会触发细胞凋亡。我们假设普遍定期审议关键组成部分，充当在动态平衡和细胞凋亡性输出，最终控制细胞命运。我们的项目目标是使用干预性方法在分子水平上研究这些开关。