Zhang Peng, Zheng Chang-Bo, Liu Xiao-Yu, Zhang Xiaowei, Huang Lingyan, Zeng Xianhai
Longgang E.N.T. Hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T, Shenzhen, Guangdong, China.
School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunan, China.
Diabet Med. 2023 Oct;40(10):e15106. doi: 10.1111/dme.15106. Epub 2023 Apr 11.
COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM.
The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments.
The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo.
Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.
2型糖尿病（T2DM）合并新型冠状病毒肺炎（COVID-19）患者的临床结局较差，死亡风险增加。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒感染需要在同一细胞中同时表达SARS-CoV-2细胞进入因子血管紧张素转换酶2（ACE2）和跨膜蛋白酶丝氨酸2型（TMPRSS2）。本研究旨在探讨T2DM患者感染COVID-19的潜在机制。
通过单细胞测序、生物信息学分析和基础实验，分析T2DM患者临床样本和糖尿病小鼠模型中不同胰腺细胞类型中AEC2和TMPRSS2的分布及表达情况。
结果显示，ACE2和TMPRSS2在人胰腺导管中表达。这些发现表明，SARS-CoV-2可通过ACE2和TMPRSS2在体内感染导管细胞。T2DM可促进外分泌导管（包括人胰腺）中ACE2和TMPRSS2的共表达。我们推测，ACE2表达水平与体内淋巴细胞数量增加有关。
血糖水平升高与ACE2表达增加及淋巴细胞数量增多有关。同时，淋巴细胞可促进ACE2表达。
