{"doi":"10.2337/db24-0816","title":"SARS-CoV-2 Spike S1 Subunit Triggers Pericyte and Microvascular Dysfunction in Human Pancreatic Islets","abstract":"The COVID-19 pandemic has profoundly affected human health; however, the mechanisms underlying its impact on metabolic and vascular systems remain incompletely understood. Clinical evidence suggests that SARS-CoV-2 directly disrupts vascular homeostasis, with perfusion abnormalities observed in various tissues. The pancreatic islet, a key endocrine miniorgan reliant on its microvasculature for optimal function, may be particularly vulnerable. Studies have proposed a link between SARS-CoV-2 infection and islet dysfunction, but the mechanisms remain unclear. Here, we investigated how SARS-CoV-2 spike S1 protein affects human islet microvascular function. Using confocal microscopy and living pancreas slices from organ donors without diabetes, we show that a SARS-CoV-2 spike S1 recombinant protein activates pericytes, key regulators of islet capillary diameter and β-cell function, and induces capillary constriction. These effects are driven by a loss of ACE2 from pericytes' plasma membrane, impairing ACE2 activity and increasing local angiotensin II levels. Our findings highlight islet pericyte dysfunction as a potential contributor to the diabetogenic effects of SARS-CoV-2 and offer new insights into the mechanisms linking COVID-19, vascular dysfunction, and diabetes. ARTICLE HIGHLIGHTS: Different components of the renin-angiotensin system are expressed by vascular cells in human pancreatic islets. The islet microvasculature is responsive to vasoactive angiotensin peptides. This pancreatic renin-angiotensin system is targeted upon incubation with a SARS-CoV-2 spike recombinant protein. SARS-CoV-2 spike activates pericytes and constricts capillaries in human islets. Islet vascular dysfunction could contribute to dysglycemia in some patients with COVID-19.","journal":"Diabetes","year":2024,"id":443928,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250520,"name":"Luciana Mateus Gonçalves","orcid":"0000-0002-1147-5066","position":1,"is_corresponding":false},{"id":288077,"name":"Elizabeth Pereira","orcid":"0000-0003-1762-3717","position":2,"is_corresponding":false},{"id":1259096,"name":"Roxana Diaz Cruz","orcid":null,"position":3,"is_corresponding":false},{"id":709977,"name":"Ruy A. Louzada","orcid":"0000-0003-1789-4234","position":4,"is_corresponding":false},{"id":290173,"name":"Maria Boulina","orcid":null,"position":5,"is_corresponding":false},{"id":7357,"name":"Joana Almaça","orcid":"0000-0002-9316-712X","position":6,"is_corresponding":false},{"id":1239473,"name":"Catarina de Andrade Barboza","orcid":"0000-0002-1096-8432","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:01:29.001453Z","pmid":"39715591","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}