Angiotensin I-Converting Enzyme type 2 expression is increased in pancreatic islets of type 2 diabetic donors

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 to a 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 at elucidating the in-situ expression pattern of ACE2 in T2D respect to non-diabetic donors which may account for a higher susceptibility to SARS-CoV-2 infection in beta-cells. Material and methods ACE2 Immunofluorescence analysis using two antibodies alongside with insulin staining was performed on FFPE pancreatic sections obtained from n=20 T2D and n=20 non-diabetic multiorgan donors. Intensity and colocalization analyses were performed on a total of 1082 pancreatic islets. Macrophages 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. ACE2 expression was increased in pancreatic islets of T2D donors in comparison to non-diabetic controls alongside with a higher colocalization rate between ACE2 and insulin using both anti-ACE2 antibodies. CD68 + cells tend 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.