SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature

Abstract

SummaryIncreasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2), is a necessary step for SARS-CoV-2 infection permissiveness. In the light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyse ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. We showed that ACE2 is indeed present in human pancreatic islets, where is preferentially expressed by insulin producing β-cells. Of note, pro-inflammatory cytokines increased ACE2 expression in β-cells, thus putatively suggesting an enhancement of β-cells sensitivity to SARS-CoV-2 during inflammatory conditions. Taken together, our data indicate a potential link between SARS-CoV-2 infection and diabetes, through direct β-cell virus tropism.Highlights-Human pancreatic islets express SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2)-In human pancreatic islets, ACE2 is preferentially expressed by β-cells-In human β-cells, ACE2 expression is increased upon inflammatory stress

Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report

“…T1DM (type 1B subtype) is not a rare condition 24 . Given the fact that ACE2 is expressed on human pancreatic β-cells 4 and that it is the main receptor for SARS-CoV-2 internalization, we propose that, in this patient, direct cytolytic β-cell damage due to SARS-CoV-2 infection resulted in insulin-dependent diabetes with no classical autoimmune pathology evident. This assumption is supported by a recent mechanistic study demonstrating that adult human pancreatic αand β-cells are permissive to SARS-CoV-2 pseudo-entry virus and SARS-CoV-2 virus infection 25 .…”

“…ACE2 is widely expressed in eukaryotic cell membranes, including those of pancreatic β-cells in mice [18][19][20] and humans 4 . Using a high-fat diet mouse model, it was shown that β-cell de-differentiation is accompanied by reduction in ACE2 (ref.…”

SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature

“…This manuscript has been released as a pre-print at https://www. biorxiv.org/content/10.1101/2020.07.23.208041v1 (84).…”

Beta-cells from patients with COVID-19 and from isolated human islets exhibit ACE2, DPP4, and TMPRSS2 expression, viral infiltration and necroptotic cell death

“…Therefore, it has been suggested that ACE2 imbalance in the pancreas causes acute beta-cell dysfunction and a resultant hyperglycemic state 14 . Furthermore, the expression of ACE2 has been shown to be increased upon inflammatory stress suggesting an enhancement of the beta-cell sensitivity to SARS-CoV-2 during inflammatory conditions 15 . Acute pancreatitis following COVID-19 has also been reported 16 .…”

“…The expression of ACE2 in the pancreas is a matter of debate and contradictory results have been reported. For example, three different studies showed a higher expression of ACE2 in the exocrine duct cells than in the islets [17][18][19] , whereas another study showed that ACE2 is preferentially expressed by beta-cells 15 . By single cell sequencing, we have shown that in pancreata from mice, both DPP4 and ACE2 are highly expressed in delta-cells followed by betaand alpha-cells (unpublished data, NATMETAB-A20093633).…”