{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:35:14Z","timestamp":1791848114048,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-15263"],"award-info":[{"award-number":["MOP-15263"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lawson Foundation","award":["MOP-15263"],"award-info":[{"award-number":["MOP-15263"]}]},{"name":"Lawson Health Research Institute","award":["MOP-15263"],"award-info":[{"award-number":["MOP-15263"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bi-hormonal islet endocrine cells have been proposed to represent an intermediate state of cellular transdifferentiation, enabling an increase in beta-cell mass in response to severe metabolic stress. Beta-cell plasticity and regenerative capacity are thought to decrease with age. We investigated the ontogeny of bi-hormonal islet endocrine cell populations throughout the human lifespan. Immunofluorescence microscopy was performed for insulin, glucagon, and somatostatin presence on paraffin-embedded sections of pancreata from 20 donors without diabetes aged between 11 days and 79 years of age. The mean proportional presence of glucagon-, insulin-, and somatostatin-immunoreactive cells within islets was 27.5%, 62.1%, and 12.1%, respectively. There was no change in the relative presence of alpha- or beta-cells with advancing age, but delta-cell presence showed a decline with age (R2 = 0.59, p &lt; 0.001). The most abundant bi-hormonal cell phenotype observed co-stained for glucagon and insulin, representing 3.1 \u00b1 0.3% of all islet cells. Glucagon\/somatostatin and insulin\/somatostatin bi-hormonal cells were also observed representing 2\u20133% abundance relative to islet cell number. Glucagon\/insulin bi-hormonal cells increased with age (R2 = 0.30, p &lt; 0.05) whilst insulin\/somatostatin (R2 = 0.50, p &lt; 0.01) and glucagon\/somatostatin (R2 = 0.35, p &lt; 0.05) cells decreased with age of donor. Findings show that bi-hormonal cells are present within human pancreatic islets throughout life, perhaps reflecting an ongoing potential for endocrine cell plasticity.<\/jats:p>","DOI":"10.3390\/cells14010034","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bi-Hormonal Endocrine Cell Presence Within the Islets of Langerhans of the Human Pancreas Throughout Life"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-1993","authenticated-orcid":false,"given":"Jiwon","family":"Hahm","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada"},{"name":"Lawson Health Research Institute, St. Joseph\u2019s Health Care, London, ON N6A 4V2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Kumar","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute, St. Joseph\u2019s Health Care, London, ON N6A 4V2, Canada"},{"name":"Faculty of Science, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Andres Fernandez","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada"},{"name":"Lawson Health Research Institute, St. Joseph\u2019s Health Care, London, ON N6A 4V2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9994-8958","authenticated-orcid":false,"given":"Edith","family":"Arany","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute, St. Joseph\u2019s Health Care, London, ON N6A 4V2, Canada"},{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2490-5678","authenticated-orcid":false,"given":"David J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada"},{"name":"Lawson Health Research Institute, St. Joseph\u2019s Health Care, London, ON N6A 4V2, Canada"},{"name":"Faculty of Science, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1210\/jc.2012-1206","article-title":"Formation of a human beta-cell population within pancreatic islets is set early in life","volume":"97","author":"Gregg","year":"2012","journal-title":"J. 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