Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Cell Metab. 2020 Dec 1;32(6):1028-1040.e4. doi: 10.1016/j.cmet.2020.11.006. Epub 2020 Nov 13.
Isolated reports of new-onset diabetes in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. This would require binding and entry of SARS-CoV-2 into β cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single β cells. In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. These findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2.
有报道称，在 COVID-19 患者中出现新发糖尿病，这导致了一种假设，即 SARS-CoV-2 直接对胰岛β细胞具有细胞毒性。这就需要 SARS-CoV-2 通过共表达其典型的细胞进入因子血管紧张素转换酶 2（ACE2）和跨膜丝氨酸蛋白酶 2（TMPRSS2）来结合并进入β细胞；然而，它们在人胰腺中的表达尚未明确界定。我们分析了 6 个人原代胰岛细胞的转录组数据集，发现 ACE2 和 TMPRSS2 在单个β细胞中并未共表达。在有和没有糖尿病的供体的胰腺切片中，β细胞中均未检测到 ACE2 和 TMPRSS2 蛋白。相反，ACE2 蛋白在胰岛和外分泌组织微血管以及一部分胰腺导管中表达，而 TMPRSS2 蛋白则局限于导管细胞。这些发现降低了 SARS-CoV-2 通过 ACE2 和 TMPRSS2 直接感染体内β细胞的可能性。
