Reports of new-onset diabetes and diabetic ketoacidosis in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2, the virus that causes COVID-19, is directly cytotoxic to pancreatic islet beta cells. This would require binding and entry of SARS-CoV-2 into host beta cells via cell surface co-expression of ACE2 and TMPRSS2, the putative receptor and effector protease, respectively. To define ACE2 and TMPRSS2 expression in the human pancreas, we examined six transcriptional datasets from primary human islet cells and assessed protein expression by immunofluorescence in pancreata from donors with and without diabetes. ACE2 and TMPRSS2 transcripts were low or undetectable in pancreatic islet endocrine cells as determined by bulk or single cell RNA sequencing, and neither protein was detected in alpha or beta cells from these donors. Instead, ACE2 protein was expressed in the islet and exocrine tissue microvasculature and also found in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. The absence of significant ACE2 and TMPRSS2 co-expression in islet endocrine cells reduces the likelihood that SARS-CoV-2 directly infects pancreatic islet beta cells through these cell entry proteins.

中文翻译：

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SARS-CoV-2 细胞进入因子 ACE2 和 TMPRSS2 在胰腺中表达，但在胰岛内分泌细胞中不丰富

有关 COVID-19 患者新发糖尿病和糖尿病酮症酸中毒的报告导致了这样的假设，即导致 COVID-19 的病毒 SARS-CoV-2 对胰岛 β 细胞具有直接细胞毒性。这将需要 SARS-CoV-2 结合并通过 ACE2 和 TMPRSS2（推定的受体和效应蛋白酶）的细胞表面共表达分别进入宿主 β 细胞。为了定义人胰腺中 ACE2 和 TMPRSS2 的表达，我们检查了来自原代人胰岛细胞的六个转录数据集，并通过免疫荧光评估了患有和未患有糖尿病的供体的胰腺中的蛋白质表达。ACE2 和 TMPRSS2 转录本在胰岛内分泌细胞中含量较低或检测不到，这通过大量或单细胞 RNA 测序确定，并且在这些供体的 α 或 β 细胞中均未检测到蛋白质。相反，ACE2 蛋白在胰岛和外分泌组织微血管系统中表达，并且也在胰管的一个子集中发现，而 TMPRSS2 蛋白仅限于导管细胞。胰岛内分泌细胞中缺乏显着的 ACE2 和 TMPRSS2 共表达降低了 SARS-CoV-2 通过这些细胞进入蛋白直接感染胰岛 β 细胞的可能性。