Lymphocytes regulate expression of the SARS-CoV-2 cell entry factor ACE2 in the pancreas of T2DM patients

Diabet Med. 2023 Oct;40(10):e15106. doi: 10.1111/dme.15106. Epub 2023 Apr 11.

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: SARS-CoV-2 cell entry factor ACE2; inflammation; lymphocytes; pancreatic ducts; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / analysis
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19* / complications
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Mice
  • Pancreas / metabolism
  • SARS-CoV-2 / physiology
  • Virus Internalization

Substances

  • Angiotensin-Converting Enzyme 2