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Article ; Online: Angiotensin I-converting enzyme type 2 expression is increased in pancreatic islets of type 2 diabetic donors.

Fignani, Daniela / Pedace, Erika / Licata, Giada / Grieco, Giuseppina Emanuela / Aiello, Elena / de Luca, Carmela / Marselli, Lorella / Marchetti, Piero / Sebastiani, Guido / Dotta, Francesco

Diabetes/metabolism research and reviews

2023  Volume 39, Issue 8, Page(s) e3696

Abstract: Aims: Angiotensin I-converting enzyme type 2 (ACE2), a pivotal SARS-CoV-2 receptor, has been shown ... to be expressed in multiple cells, including human pancreatic beta-cells. A putative bidirectional ... However, whether ACE2 expression levels are altered in beta-cells of diabetic patients has not yet been investigated ...

Abstract Aims: Angiotensin I-converting enzyme type 2 (ACE2), a pivotal SARS-CoV-2 receptor, has been shown to be expressed in multiple cells, including human pancreatic beta-cells. A putative bidirectional relationship between SARS-CoV-2 infection and diabetes has been suggested, confirming the hypothesis that viral infection in beta-cells may lead to new-onset diabetes or worse glycometabolic control in diabetic patients. However, whether ACE2 expression levels are altered in beta-cells of diabetic patients has not yet been investigated. Here, we aimed to elucidate the in situ expression pattern of ACE2 in Type 2 diabetes (T2D) with respect to non-diabetic donors which may account for a higher susceptibility to SARS-CoV-2 infection in beta-cells.
Material and methods: Angiotensin I-converting enzyme type 2 immunofluorescence analysis using two antibodies alongside insulin staining was performed on formalin-fixed paraffin embedded pancreatic sections obtained from n = 20 T2D and n = 20 non-diabetic (ND) multiorgan donors. Intensity and colocalisation analyses were performed on a total of 1082 pancreatic islets. Macrophage detection was performed using anti-CD68 immunohistochemistry on serial sections from the same donors.
Results: Using two different antibodies, ACE2 expression was confirmed in beta-cells and in pancreas microvasculature. Angiotensin I-converting enzyme type 2 expression was increased in pancreatic islets of T2D donors in comparison to ND controls alongside with a higher colocalisation rate between ACE2 and insulin using both anti-ACE2 antibodies. CD68
Conclusions: Higher ACE2 expression in T2D islets might increase their susceptibility to SARS-CoV-2 infection during COVID-19 in T2D patients, thus worsening glycometabolic outcomes and disease severity.
MeSH term(s) Humans ; Angiotensin-Converting Enzyme 2 ; COVID-19/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Insulin/metabolism ; Islets of Langerhans/metabolism ; Peptidyl-Dipeptidase A
Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Insulin ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23)
Language English
Publishing date 2023-07-19
Publishing country England
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 1470192-3
ISSN 1520-7560 ; 1520-7552
ISSN (online) 1520-7560
ISSN 1520-7552
DOI 10.1002/dmrr.3696
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