Department of Pathology, Immunology, and Laboratory Medicine, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL 32610, USA.
Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Cell Metab. 2020 Dec 1;32(6):1041-1051.e6. doi: 10.1016/j.cmet.2020.11.005. Epub 2020 Nov 13.
Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
糖尿病与严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的死亡率增加有关。鉴于文献表明 SARS-CoV-2 感染与糖尿病诱导之间存在潜在关联，我们研究了胰腺中血管紧张素转换酶 2（ACE2）的表达，ACE2 是 SARS-CoV-2 感染的关键进入因素。具体来说，我们分析了五个公共 scRNA-seq 胰腺数据集，并进行了荧光原位杂交、western blot 和 ACE2 的免疫定位，对跨越整个生命周期的正常人类胰腺组织以及来自 2019 年冠状病毒病（COVID-19）病例的组织进行了广泛的试剂验证。这些计算机分析和体外分析表明，ACE2 在胰腺导管上皮和微血管中表达明显，但我们发现内分泌细胞的 mRNA 水平表达很少。COVID-19 患者的胰腺显示出多种血栓病变，SARS-CoV-2 核衣壳蛋白表达主要局限于导管。这些结果表明，SARS-CoV-2 通过 ACE2 感染胰腺内分泌细胞不太可能是 COVID-19 相关糖尿病的主要致病特征。
