Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Sci Rep. 2020 Dec 18;10(1):22315. doi: 10.1038/s41598-020-79313-y.
In experimental studies, pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects. Even so, almost no information is available concerning human islet microvascular endothelial cell (MVEC) physiology and gene expression. In this study, islets and exocrine pancreatic tissue were acquired from organ donors with normoglycemia or impaired glucose metabolism (IGM) immediately after islet isolation. Following single-cell dissociation, primary islet- and exocrine MVECs were obtained through fluorescence-activated cell sorting (FACS) and transcriptional profiles were generated using AmpliSeq. Multiple gene sets involved in general vascular development and extracellular matrix remodeling were enriched in islet MVEC. In exocrine MVEC samples, multiple enriched gene sets that relate to biosynthesis and biomolecule catabolism were found. No statistically significant enrichment was found in gene sets related to autophagy or endoplasmic reticulum (ER) stress. Although ample differences were found between islet- and exocrine tissue endothelial cells, no differences could be observed between normoglycemic donors and donors with IGM at gene or gene set level. Our data is consistent with active angiogenesis and vascular remodeling in human islets and support the notion of ongoing endocrine pancreas tissue repair and regeneration even in the adult human.
在实验研究中，胰岛微血管对于胰岛内分泌功能和质量至关重要，并且糖尿病患者的胰岛血管形态发生改变。即便如此，关于人类胰岛微血管内皮细胞（MVEC）的生理学和基因表达，几乎没有信息。在这项研究中，从血糖正常或葡萄糖代谢受损（IGM）的器官捐献者中获得胰岛和外分泌胰腺组织，在胰岛分离后立即获得。通过荧光激活细胞分选（FACS）进行单细胞解离后，获得原代胰岛和外分泌 MVEC，并使用 AmpliSeq 生成转录谱。多个涉及一般血管发育和细胞外基质重塑的基因集在外分泌 MVEC 样本中富集。在外分泌 MVEC 样本中，发现了多个与生物合成和生物分子分解代谢相关的富集基因集。在与自噬或内质网（ER）应激相关的基因集方面未发现统计学上显著的富集。尽管在胰岛和外分泌组织内皮细胞之间发现了大量差异，但在基因或基因集水平上，在血糖正常的供体和 IGM 供体之间没有差异。我们的数据与人类胰岛中的活跃血管生成和血管重塑一致，并支持即使在成年人体内，内分泌胰腺组织修复和再生仍在进行的观点。
