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Restoring functional \u03b2\u2010cell mass whether through replication of existing \u03b2\u2010cells, neogenesis from alternative cellular sources, or protection of stressed cells remains a central therapeutic goal. In this review article, we synthesize evidence from rodent and human studies under normal physiology to highlight how \u03b2\u2010cell mass is established, maintained, and adapted. We emphasize the steep decline in proliferative capacity after early life, the long lifespan of adult \u03b2\u2010cells, and the limited, context\u2010dependent adaptations observed in obesity, pregnancy, insulin resistance, and impaired glucose tolerance. Beyond apoptosis, \u03b2\u2010cell dedifferentiation has emerged as a key mechanism of functional decline, whereby mature \u03b2\u2010cells lose identity, revert to a progenitor\u2010like state, and contribute to reduced insulin output. We also examine cell\u2010intrinsic brakes on proliferation, the trophic roles of incretins and growth factors, and the debated contribution of neogenesis and transdifferentiation from ductal, acinar, or non\u2010\u03b2 endocrine lineages. Advances in \u03b2\u2010cell mass quantification, including glucagon\u2010like peptide\u20101 (GLP\u20101) receptor\u2010targeted imaging, are discussed alongside methodological challenges in human tissue studies. Finally, we review therapeutic avenues such as GLP\u20101 receptor agonists (GLP\u20101RAs) that mitigate ER and oxidative stress, restore autophagy, and preserve functional mass. Together, these insights frame testable strategies to prevent \u03b2\u2010cell failure and guide diabetes therapies.<\/jats:p>","DOI":"10.1111\/dom.70191","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:26:50Z","timestamp":1761762410000},"page":"27-49","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pancreatic \u03b2\u2010cell turnover in health and disease"],"prefix":"10.1111","volume":"28","author":[{"given":"Yasmine","family":"Alcibahy","sequence":"first","affiliation":[{"name":"School of Medicine Royal College of Surgeons in Ireland, Bahrain  Adliya Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radwan","family":"Darwish","sequence":"additional","affiliation":[{"name":"School of Medicine Royal College of Surgeons in Ireland, Bahrain  Adliya Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies and Research Royal College of Surgeons in Ireland, Bahrain  Adliya Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-2501","authenticated-orcid":false,"given":"Abu Saleh Md","family":"Moin","sequence":"additional","affiliation":[{"name":"School of Postgraduate Studies and Research Royal College of Surgeons in Ireland, Bahrain  Adliya 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