title: Destruction of tissue, cells and organelles in type 1 diabetic rats presented at macromolecular resolution.
abstract: 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.
authors: Dept. Molecular Cell Biology, Leiden University Medical Center, P. O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors: Raimond B G
authors: RB
authors: Ravelli
authors: Ruby D
authors: RD
authors: Kalicharan
authors: M Cristina
authors: MC
authors: Avramut
authors: Klaas A
authors: KA
authors: Sjollema
authors: Joachim W
authors: JW
authors: Pronk
authors: Freark
authors: F
authors: Dijk
authors: Abraham J
authors: AJ
authors: Koster
authors: Jeroen T J
authors: JT
authors: Visser
authors: Frank G A
authors: FG
authors: Faas
authors: Ben N G
authors: BN
authors: Giepmans
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D055098:Endocrine Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006003:Glycogen / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron / Q000379:methods; D051381:Rats
chemical_list: D007328:Insulin; D006003:Glycogen
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