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. 2023 Nov;39(8):e3696.
doi: 10.1002/dmrr.3696. Epub 2023 Jul 19.

Angiotensin I-converting enzyme type 2 expression is increased in pancreatic islets of type 2 diabetic donors

Daniela Fignani  1   2 , Erika Pedace  1   2 , Giada Licata  1   2 , Giuseppina Emanuela Grieco  1   2 , Elena Aiello  1   2 , Carmela de Luca  3 , Lorella Marselli  3 , Piero Marchetti  4 , Guido Sebastiani  1   2 , Francesco Dotta  1   2   5
Affiliations

Angiotensin I-converting enzyme type 2 expression is increased in pancreatic islets of type 2 diabetic donors

Daniela Fignani et al. Diabetes Metab Res Rev. 2023 Nov.

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+ cells tended to be increased in T2D pancreata, in line with higher ACE2 expression observed in serial sections.

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.

Keywords: ACE2; COVID-19; SARS-CoV-2; beta-cell; pancreatic islets; type 2 diabetes.

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References

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