Destruction of Tissue, Cells and Organelles in Type 1 Diabetic Rats Presented at Macromolecular Resolution
Destruction of Tissue, Cells and Organelles in Type 1 Diabetic Rats Presented at Macromolecular Resolution
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DOI：
10.1038/srep01804
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发表时间：
2013-05-08
影响因子：
4.6
通讯作者：
Giepmans, Ben N. G.
中科院分区：
文献类型：
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作者：
Ravelli, Raimond B. G.;Kalicharan, Ruby D.;Giepmans, Ben N. G.
寻找胰岛素治疗的替代方案和1型糖尿病病因学的进展受益于对朗格汉斯胰岛的全面结构和功能的了解。电子显微镜（EM）可以在尽可能高的分辨率下可视化胰岛形态，然而，传统的EM只能提供有偏差的快照，缺乏背景。我们开发并使用了大规模的EM，并编制了大鼠胰岛在免疫破坏过程中的完整横截面资源，以在大分子分辨率上提供数千个细胞的无偏见结构洞察。该资源包括6个数据集，总计25000张显微照片，对自身免疫性糖尿病期间的细胞和超微结构变化进行了注释。粒细胞被吸引到内分泌组织，接着是白细胞的外渗。β细胞的亚细胞变化包括内质网应激、胰岛素脱肉芽和糖原积累。罕见的表现包括红细胞外渗和核肌动蛋白样纤维。虽然我们专注于自身免疫性糖尿病的大鼠模型，但我们的方法是普遍适用的。
Finding alternatives for insulin therapy and making advances in etiology of type 1 diabetes benefits from a full structural and functional insight into Islets of Langerhans. Electron microscopy (EM) can visualize Islet morphology at the highest possible resolution, however, conventional EM only provides biased snapshots and lacks context. We developed and employed large scale EM and compiled a resource of complete cross sections of rat Islets during immuno-destruction to provide unbiased structural insight of thousands of cells at macromolecular resolution. The resource includes six datasets, totalling 25.000 micrographs, annotated for cellular and ultrastructural changes during autoimmune diabetes. Granulocytes are attracted to the endocrine tissue, followed by extravasation of a pleiotrophy of leukocytes. Subcellullar changes in beta cells include endoplasmic reticulum stress, insulin degranulation and glycogen accumulation. Rare findings include erythrocyte extravasation and nuclear actin-like fibers. While we focus on a rat model of autoimmune diabetes, our approach is general applicable.