{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T10:31:49Z","timestamp":1782556309970,"version":"3.54.5"},"reference-count":58,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["AWD-007061"],"award-info":[{"award-number":["AWD-007061"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK133483"],"award-info":[{"award-number":["DK133483"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK138471"],"award-info":[{"award-number":["DK138471"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["3-PDF-2024-1503-A-N"],"award-info":[{"award-number":["3-PDF-2024-1503-A-N"]}],"id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK135017"],"award-info":[{"award-number":["DK135017"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>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 \u03b2-cell function, and induces capillary constriction. These effects are driven by a loss of ACE2 from pericytes\u2019 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db24-0816","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T22:53:17Z","timestamp":1734994397000},"page":"355-367","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":8,"title":["SARS-CoV-2 Spike S1 Subunit Triggers Pericyte and Microvascular Dysfunction in Human Pancreatic Islets"],"prefix":"10.2337","volume":"74","author":[{"given":"Catarina","family":"Andrade Barboza","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Mateus","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Pereira","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"},{"name":"2Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana Diaz","family":"Cruz","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruy","family":"Andrade Louzada","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Boulina","sequence":"additional","affiliation":[{"name":"3Diabetes Research Institute, University of Miami Health System, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-712X","authenticated-orcid":false,"given":"Joana","family":"Alma\u00e7a","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL"},{"name":"2Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL"},{"name":"3Diabetes Research Institute, University of Miami Health System, Miami, FL"},{"name":"4Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"2025022019523428400_B1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"2025022019523428400_B2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S2213-8587(20)30272-2","article-title":"Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study","volume":"8","author":"Barron","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025022019523428400_B3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S2213-8587(20)30271-0","article-title":"Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study","volume":"8","author":"Holman","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2025022019523428400_B4","doi-asserted-by":"crossref","first-page":"2491.e3","DOI":"10.1016\/j.ajem.2020.05.114","article-title":"Newly diagnosed diabetes and diabetic ketoacidosis precipitated by COVID-19 infection","volume":"38","author":"Heaney","year":"2020","journal-title":"Am J Emerg Med"},{"key":"2025022019523428400_B5","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s42255-020-00281-8","article-title":"Autoantibody-negative insulin-dependent diabetes mellitus after SARS-CoV-2 infection: a case report","volume":"2","author":"Hollstein","year":"2020","journal-title":"Nat Metab"},{"key":"2025022019523428400_B6","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/s42255-021-00407-6","article-title":"Acute and long-term disruption of glycometabolic control after SARS-CoV-2 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Current evidence","volume":"23","author":"Wong","year":"2023","journal-title":"Curr Diab Rep"},{"key":"2025022019523428400_B10","doi-asserted-by":"crossref","first-page":"e1009","DOI":"10.1210\/clinem\/dgab792","article-title":"No evidence of long-term disruption of glycometabolic control after SARS-CoV-2 infection","volume":"107","author":"Laurenzi","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2025022019523428400_B11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"2025022019523428400_B12","doi-asserted-by":"crossref","first-page":"e9610","DOI":"10.15252\/msb.20209610","article-title":"The protein expression profile of ACE2 in human tissues","volume":"16","author":"Hikmet","year":"2020","journal-title":"Mol Syst 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Reports"},{"key":"2025022019523428400_B28","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1093\/cvr\/cvaa078","article-title":"The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2","volume":"116","author":"Chen","year":"2020","journal-title":"Cardiovasc Res"},{"key":"2025022019523428400_B29","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","article-title":"SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues","volume":"181","author":"Ziegler","year":"2020","journal-title":"Cell"},{"key":"2025022019523428400_B30","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1038\/s41591-021-01443-1","article-title":"A human three-dimensional neural-perivascular \u2018assembloid\u2019 promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology","volume":"27","author":"Wang","year":"2021","journal-title":"Nat Med"},{"key":"2025022019523428400_B31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev-physiol-031522-034807","article-title":"Pericytes and the control of blood flow in brain and heart","volume":"85","author":"Longden","year":"2023","journal-title":"Annu Rev Physiol"},{"key":"2025022019523428400_B32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1369\/00221554241236535","article-title":"Diabetes as a pancreatic microvascular disease\u2014a pericytic perspective","volume":"72","author":"Mateus Gon\u00e7alves","year":"2024","journal-title":"J Histochem Cytochem"},{"key":"2025022019523428400_B33","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00268-006-0719-8","article-title":"Islet vasculature as a regulator of endocrine pancreas function","volume":"31","author":"Ballian","year":"2007","journal-title":"World J 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vasoconstrictive effects","volume":"64","author":"Sauter","year":"2015","journal-title":"Diabetes"},{"key":"2025022019523428400_B55","doi-asserted-by":"crossref","first-page":"377","DOI":"10.14348\/molcells.2021.0094","article-title":"Experimental models for SARS-CoV-2 infection","volume":"44","author":"Kim","year":"2021","journal-title":"Mol Cells"},{"key":"2025022019523428400_B56","doi-asserted-by":"crossref","first-page":"e3565","DOI":"10.1002\/dmrr.3565","article-title":"Inflammation and vascular dysfunction: the negative synergistic combination of diabetes and COVID-19","volume":"38","author":"Bolla","year":"2022","journal-title":"Diabetes Metab Res Rev"},{"key":"2025022019523428400_B57","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.2337\/db21-0926","article-title":"Indirect and direct effects of SARS-CoV-2 on human pancreatic islets","volume":"71","author":"Ben 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