小柯机器人

以色列耶路撒冷的希伯来大学Yuval Dor和Agnes Klochendler合作取得重要工作进展。他们研究提出，β细胞中RNA编辑酶的紊乱模拟了早期1型糖尿病。相关研究成果2023年12月20日在线发表于《细胞—代谢》杂志上。

据介绍，1型糖尿病（T1D）病因的一个主要假设是由病毒感染引发，导致双链RNA（dsRNA）介导的干扰素反应和炎症；然而，这种假设的致病病毒尚未被确定。

研究人员使用小鼠模型，与人类胰岛数据相证实，证明β细胞中的内源性dsRNA可以导致糖尿病性免疫反应，从而确定了不依赖病毒的T1D启动机制。研究人员发现，β细胞中作用于RNA的RNA编辑酶腺苷脱氨酶（ADAR）的破坏会引发大规模干扰素反应、胰岛炎症、β细胞衰竭和破坏，其特征与早期人类T1D惊人相似。通过钙介导的糖酵解增强了干扰素响应，表明存在一个可操作的炎症和胰岛β细胞负担增加的恶性循环。

附：英文原文

Title: Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes

Author: Udi Ehud Knebel, Shani Peleg, Chunhua Dai, Roni Cohen-Fultheim, Sara Jonsson, Karin Poznyak, Maya Israeli, Liza Zamashanski, Benjamin Glaser, Erez Y. Levanon, Alvin C. Powers, Agnes Klochendler, Yuval Dor

Issue&Volume: 2023-12-20

Abstract: A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) in beta cells triggers a massive interferon response, islet inflammation, and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload.

DOI: 10.1016/j.cmet.2023.11.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00443-6

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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