2095-LB: Impact of SARS-CoV-2 Spike Proteins on the Islet Microvascular Function

Introduction: The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). We hypothesized that SARS-CoV-2 could trigger loss of glucose homeostasis by compromising microvascular function in the pancreas.

Methods: We incubated living pancreas slices from 7 non-diabetic human donors (from nPOD) with SARS-CoV-2 Spike S1 recombinant protein (SARS-Spike; 80 nM, 5xEC₅₀, 1h). As a control, we incubated slices with a Spike S1 protein from HCoV-OC43. By confocal microscopy, we monitored the acute effects of these Spike S1 proteins on pericyte [Ca²⁺]i responses and vasomotion (capillaries labeled with fluorescent lectin). Using an ELISA assay, we assessed the effect of Spike S1 proteins on the endogenous levels of angiotensin II and angiotensin 1-7 in the supernatant of human pancreas slices.

Results: Acute incubation with SARS-Spike led to closure of capillaries in human islets in living slices. We then stimulated slices with angiotensin II (100 nM; for 4 min) in 3 mM glucose solution. While islet capillaries in slices incubated with HCoV-OC43 constricted upon Angiotensin II application (~14% average reduction in diameter), vessels in slices treated with SARS-Spike did not further respond to Angiotensin II stimulation. In addition, incubation with SARS-Spike decreased the stimulatory effect of Angiotensin II on islet pericyte cytosolic calcium levels. Incubation with SARS-Spike slightly increased the levels of Angiotensin II produced by living pancreas slices while there was no difference in Angiotensin1-7 concentration.

Conclusion: Our data indicate that the potential infection of vascular cells by SARS-CoV-2 could interfere with pericytes’ contractile properties and compromise capillary responses. We will determine in the future whether these changes are associated with an inhibition of ACE2 and/or a reduction of its expression at the plasma membrane.