{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:37:34Z","timestamp":1789771054880,"version":"4.0.1"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["RD Lawrence Research Fellowship"],"award-info":[{"award-number":["RD Lawrence Research Fellowship"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"publisher","award":["Vice-Chancellor PhD studentship"],"award-info":[{"award-number":["Vice-Chancellor PhD studentship"]}],"id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clin Med Insights Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Pregnancy induces a reversible expansion of pancreatic islet and beta-cell mass, but the impact of multiple pregnancies on these processes remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      To further investigate this phenomenon, the current study employed transgenic models with beta- or alpha-cell lineage tracing capabilities, namely Ins1\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">Cre\/+<\/jats:italic>\n                      <\/jats:sup>\n                      ;Rosa26-eYFP and Glu\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">CreERT2<\/jats:italic>\n                      <\/jats:sup>\n                      ;Rosa26-eYFP male mice, respectively. Using these models, we explored late-stage morphological islet adaptations and cellular plasticity in response to primi-, bi- and tri-parity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      All pregnant mice exhibited augmented islet and beta-cell areas, associated with decreased beta-cell apoptosis and increased proliferation. Notably, beta-cell proliferative capacity decreased as parity increased, but was still elevated in triparous mice when compared to null parous controls. Interestingly, alpha-cells also exhibited augmented growth and survival in all pregnant mice. In terms of cellular transdifferentiation, ductal to beta-cell conversion appeared greater in primiparous Ins1\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">Cre\/+<\/jats:italic>\n                      <\/jats:sup>\n                      ;Rosa26-eYFP mice, but was much less obvious in bi- and tri-parous mice. Whilst quantification of beta- to alpha-cell transition events was more pronounced during pregnancy, it was less obvious in multiparity than primiparity. There were also notable reductions in beta-cell dedifferentiation, supporting positive effects of islet cell plasticity towards retention and expansion of beta-cell mass in multiparity. In harmony, alpha- to beta-cell transdifferentiation appeared markedly increased in multiparous Glu\n                      <jats:sup>\n                        <jats:italic toggle=\"yes\">CreERT2<\/jats:italic>\n                      <\/jats:sup>\n                      ;Rosa26-eYFP mice, coupled with augmented alpha-cell neogenesis and dedifferentiation, suggesting that these cells act as a principal source for beta-cell expansion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Together, these findings indicate that reduced beta-cell proliferation in multiparity is offset by enhanced islet cell plasticity, contributing to sustained islet adaptation across multiple gestations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11795514251386124","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:38:57Z","timestamp":1760765937000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Multiparity on Pregnancy-Induced Islet Adaptation and Cellular Transdifferentiation"],"prefix":"10.1177","volume":"18","author":[{"given":"Vaibhav","family":"Dubey","sequence":"first","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Tanday","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Ali","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei I.","family":"Tarasov","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-964X","authenticated-orcid":false,"given":"Nigel","family":"Irwin","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Charlotte","family":"Moffett","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, Schools of Biomedical Sciences and Pharmacy &amp; Pharmaceutical Sciences, Ulster University, Coleraine, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0144"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12716"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113467"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2217\/dmt.10.24"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP281082"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01443.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0862-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2016-000237"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01100-2"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13552"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/dme.15434"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3384"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1477"},{"issue":"5","key":"e_1_3_2_15_2","first-page":"231","article-title":"Mechanisms in endocrinology: parity and risk of type 2 diabetes: a systematic review and dose-response meta-analysis","volume":"175","author":"Li PY","year":"2016","unstructured":"Li PY, Shan ZL, Zhou L, et al. Mechanisms in endocrinology: parity and risk of type 2 diabetes: a systematic review and dose-response meta-analysis. 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