{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:53:31Z","timestamp":1782280411465,"version":"3.54.5"},"posted":{"date-parts":[[2025,5,18]]},"group-title":"Pathology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,18]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>A high-definition description of pancreatic islets would prove beneficial for understanding the pathophysiology of type 1 diabetes (T1D), yet significant knowledge voids exist in terms of their size, endocrine cell composition, and number in both health and disease. Here, 3-dimensional (3D) analyses of pancreata from control persons without diabetes (ND) revealed heretofore underappreciated frequencies (approximately 50%) of insulin-positive (INS+) glucagon-negative (GCG-) islets. Non-diabetic individuals positive for a single Glutamic acid decarboxylase autoantibody (GADA+) yet at increased risk for disease consistently demonstrated endocrine features, including islet volume and cell composition, closely resembling the age-matched ND controls. In contrast, pancreata from individuals with short-duration T1D demonstrated significantly reduced islet density and a dramatic loss of INS+GCG- islets with preservation of large INS+GCG+ islets. The size and cellular composition of pancreatic islets may, therefore, represent influential factors that impact \u03b2-cell loss during T1D disease progression.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"654045v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>3D imaging of non-diabetic (ND) pancreas suggests up to 50% of INS+ islets lack GCG<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>INS+GCG- islets are typically small-sized in ND and preferentially lost in T1D<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>In T1D pancreas, INS+ beta cells are preserved in large INS+GCG+ islets<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Islets from GADA+ individuals appear similar to ND for size and \u03b2-to-\u03b1 cell ratios<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.14.654045","type":"posted-content","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T01:30:10Z","timestamp":1747618210000},"source":"Crossref","is-referenced-by-count":3,"title":["3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7300-8466","authenticated-orcid":false,"given":"Alexandra","family":"Rippa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-0958","authenticated-orcid":false,"given":"Amanda L.","family":"Posgai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Currlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maigan","family":"Brusko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MacKenzie D.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Kaddis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kusmartseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive H.","family":"Wasserfall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Campbell-Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025052103550640000_2025.05.14.654045v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05203-7"},{"key":"2025052103550640000_2025.05.14.654045v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/2025.03.18.644000"},{"key":"2025052103550640000_2025.05.14.654045v1.3","doi-asserted-by":"publisher","DOI":"10.2337\/db15-0779"},{"key":"2025052103550640000_2025.05.14.654045v1.4","doi-asserted-by":"publisher","DOI":"10.2337\/db16-1343"},{"key":"2025052103550640000_2025.05.14.654045v1.5","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0421"},{"key":"2025052103550640000_2025.05.14.654045v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-019-01353-2"},{"key":"2025052103550640000_2025.05.14.654045v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.717101"},{"key":"2025052103550640000_2025.05.14.654045v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4772-2"},{"key":"2025052103550640000_2025.05.14.654045v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114346"},{"key":"2025052103550640000_2025.05.14.654045v1.10","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7030054"},{"key":"2025052103550640000_2025.05.14.654045v1.11","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718779898"},{"key":"2025052103550640000_2025.05.14.654045v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/srep14634"},{"key":"2025052103550640000_2025.05.14.654045v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47686-7"},{"key":"2025052103550640000_2025.05.14.654045v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02589-x"},{"key":"2025052103550640000_2025.05.14.654045v1.15","doi-asserted-by":"publisher","DOI":"10.1080\/19382014.2015.1024405"},{"key":"2025052103550640000_2025.05.14.654045v1.16","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000025642"},{"key":"2025052103550640000_2025.05.14.654045v1.17","doi-asserted-by":"publisher","DOI":"10.2337\/db19-0072"},{"key":"2025052103550640000_2025.05.14.654045v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.018"},{"key":"2025052103550640000_2025.05.14.654045v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-024-00478-y"},{"key":"2025052103550640000_2025.05.14.654045v1.20","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419"},{"key":"2025052103550640000_2025.05.14.654045v1.21","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14080878"},{"key":"2025052103550640000_2025.05.14.654045v1.22","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1208"},{"key":"2025052103550640000_2025.05.14.654045v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.11.014"},{"key":"2025052103550640000_2025.05.14.654045v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-018-1084-3"},{"key":"2025052103550640000_2025.05.14.654045v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74616-6"},{"key":"2025052103550640000_2025.05.14.654045v1.26","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06143-2"},{"key":"2025052103550640000_2025.05.14.654045v1.27","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.644826"},{"key":"2025052103550640000_2025.05.14.654045v1.28","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz9124"},{"key":"2025052103550640000_2025.05.14.654045v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85659-8"},{"key":"2025052103550640000_2025.05.14.654045v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05614-4"},{"key":"2025052103550640000_2025.05.14.654045v1.31","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.11.648319"},{"key":"2025052103550640000_2025.05.14.654045v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.04.002"},{"key":"2025052103550640000_2025.05.14.654045v1.33","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo3932"},{"key":"2025052103550640000_2025.05.14.654045v1.34","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3756"},{"key":"2025052103550640000_2025.05.14.654045v1.35","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0416"},{"key":"2025052103550640000_2025.05.14.654045v1.36","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab010"},{"key":"2025052103550640000_2025.05.14.654045v1.37","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.5C6684.2005"},{"key":"2025052103550640000_2025.05.14.654045v1.38","doi-asserted-by":"publisher","DOI":"10.4161\/isl.2.3.11815"},{"key":"2025052103550640000_2025.05.14.654045v1.39","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.140"},{"key":"2025052103550640000_2025.05.14.654045v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3043-5"},{"key":"2025052103550640000_2025.05.14.654045v1.41","doi-asserted-by":"publisher","DOI":"10.2337\/diab.14.10.619"},{"key":"2025052103550640000_2025.05.14.654045v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.01.003"},{"key":"2025052103550640000_2025.05.14.654045v1.43","doi-asserted-by":"publisher","DOI":"10.4161\/isl.24780"},{"key":"2025052103550640000_2025.05.14.654045v1.44","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-017-0915-y"},{"key":"2025052103550640000_2025.05.14.654045v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/bf00252762"},{"key":"2025052103550640000_2025.05.14.654045v1.46","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.20.629754"},{"key":"2025052103550640000_2025.05.14.654045v1.47","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-018-1083-4"},{"key":"2025052103550640000_2025.05.14.654045v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3159-7"},{"key":"2025052103550640000_2025.05.14.654045v1.49","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12797"},{"key":"2025052103550640000_2025.05.14.654045v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.010"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.14.654045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:02:32Z","timestamp":1782277352000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.14.654045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,18]]},"references-count":50,"URL":"https:\/\/doi.org\/10.1101\/2025.05.14.654045","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41467-025-66198-6","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,5,18]]},"subtype":"preprint"}}