Abstract
Background: Pregnancy induces a reversible expansion of pancreatic islet and beta-cell mass, but the impact of multiple pregnancies on these processes remains unclear.
Methods: To further investigate this phenomenon, the current study employed transgenic models with beta- or alpha-cell lineage tracing capabilities, namely Ins1Cre/+ ;Rosa26-eYFP and GluCreERT2;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.
Results: 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 Ins1Cre/+;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 GluCreERT2 ;Rosa26-eYFP mice, coupled with augmented alpha-cell neogenesis and dedifferentiation, suggesting that these cells act as a principal source for beta-cell expansion.
Conclusion: 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.
Methods: To further investigate this phenomenon, the current study employed transgenic models with beta- or alpha-cell lineage tracing capabilities, namely Ins1Cre/+ ;Rosa26-eYFP and GluCreERT2;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.
Results: 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 Ins1Cre/+;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 GluCreERT2 ;Rosa26-eYFP mice, coupled with augmented alpha-cell neogenesis and dedifferentiation, suggesting that these cells act as a principal source for beta-cell expansion.
Conclusion: 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1-8 |
| Number of pages | 8 |
| Journal | Clinical Medicine Insights: Endocrinology and Diabetes |
| Volume | 18 |
| Early online date | 17 Oct 2025 |
| DOIs | |
| Publication status | Published online - 17 Oct 2025 |
Bibliographical note
Publisher Copyright:© The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Data Access Statement
All data used to support the findings of this study are available from the lead scientist (VD) upon request.Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: These studies were supported by an Ulster University ViceChancellor PhD studentship awarded to VD and Diabetes UK RD Lawrence Research Fellowship awarded to RCM.
Keywords
- beta-cell
- islet morphology
- transdifferentiation
- islet
- multiparity
- cell lineage