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标题：Islet Macrophages Shift to a Reparative State following Pancreatic Beta-Cell Death and Are a Major Source of Islet Insulin-like Growth Factor-1
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作者：Dominika Nackiewicz ; Meixia Dan ; Madeleine Speck 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：1
页码：1-47
DOI：10.1016/j.isci.2019.100775
语种：English
出版社：Elsevier
摘要：SummaryMacrophages play a dynamic role in tissue repair following injury. Here we found that following streptozotocin (STZ)-induced beta-cell death, mouse islet macrophages had increasedIgf1expression, decreased proinflammatory cytokine expression, and transcriptome changes consistent with macrophages undergoing efferocytosis and having an enhanced state of metabolism. Macrophages were the major, if not sole, contributors to islet insulin-like growth factor-1 (IGF-1) production. Adoptive transfer experiments showed that macrophages can maintain insulin secretionin vivofollowing beta-cell death with no effects on islet cell turnover. IGF-1 neutralization during STZ treatment decreased insulin secretion without affecting islet cell apoptosis or proliferation. Interestingly, high-fat diet (HFD) combined with STZ further skewed islet macrophages to a reparative state. Finally, islet macrophages fromdb/dbmice also expressed decreased proinflammatory cytokines and increasedIgf1mRNA. These data have important implications for islet biology and pathology and show that islet macrophages preserve their reparative state following beta-cell death even during HFD feeding and severe hyperglycemia.Graphical AbstractDisplay OmittedHighlights•Macrophages are a major source of IGF-1 protein within mouse pancreatic islets•Post-beta-cell death islet macrophages shift to a reparative state•Beta-cell death causes macrophage transcriptome changes consistent with efferocytosis•This change can occur even in the presence of HFD feeding or severe hyperglycemiaDiabetology; Immunology; Specialized Functions of Cells