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

Author:

Fignani Daniela12ORCID,Pedace Erika12ORCID,Licata Giada12ORCID,Grieco Giuseppina Emanuela12ORCID,Aiello Elena12ORCID,de Luca Carmela3,Marselli Lorella3,Marchetti Piero4,Sebastiani Guido12ORCID,Dotta Francesco125ORCID

Affiliation:

1. Diabetes and Metabolic Disease Unit Department of Medicine, Surgery and Neurosciences University of Siena Siena Italy

2. Fondazione Umberto Di Mario C/o Toscana Life Sciences Siena Italy

3. Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy

4. Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

5. Tuscany Centre for Precision Medicine (CReMeP) Siena Italy

Abstract

AbstractAimsAngiotensin 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 MethodsAngiotensin 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.ResultsUsing 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.ConclusionsHigher 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.

Publisher

Wiley

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine

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