Background and aims: Stimulation of beta cell formation and transplantation offer hope as diabetes treatments. Yet, lack of knowledge in the mechanisms of postnatal islet growth hampers their implementation. The major mechanism of beta cell maintenance in adults is shown to be self-duplication. However, beta cell neogenesis from non-beta cells might still take place under other conditions e.g. during the neonatal period. Previously, indirect evidence was reported for beta cell neogenesis in this early period of life. More recently, a tracing study suggested generation of beta cells from non-beta cells neonatally. Methods: To quantify neonatal beta cell neogenesis we used transgenic RIPCreER Rosa26LoxSTOPLoxYFP mice. Pups received tamoxifen intraperitoneally on the day of birth and were followed during the next four weeks. Results: In tamoxifen-treated mice, beta cells are labelled with a high efficiency and specificity. 84.0 ± 0.4% beta cells express YFP at postnatal day 7. Without tamoxifen, there is only limited ‘leaky’ expression. From week 1 to week 4, there is a 3-fold increase in the beta cell mass. The non-fasting glycaemia remains normal throughout this period both in tamoxifen and non-tamoxifen animals. The islet size distribution shows a decrease in the fraction of small islets (1-5 beta cells) and an increase in the fraction of larger islets (11-50 beta cells and >50 beta cells). To quantify beta cell neogenesis, tamoxifen-treated mice from week 1 were compared with week 4. The percentage YFP+ beta cells, representing pre-existing beta cells or their progeny, decreases significantly during the neonatal development. About 20-25% of the beta cells at week 4 are newly formed from progenitor cells. Both in small clusters and in islets a decrease in YFP+ beta cells is observed. Conclusion: We have obtained direct evidence via genetic lineage tracing which confirms that beta cell neogenesis occurs in young mice.
|Titel||Poster presentation EASD Islet Study Group annual meeting ISG2013|
|Subtitel||Beta cell regeneration and genome regulation|
|Status||Published - 27 sep 2013|
|Evenement||EASD Islet Study Group annual meeting ISG2013: Beta cell regeneration and genome regulation - Sitges, Spain|
Duur: 27 sep 2013 → 29 sep 2013
|Conference||EASD Islet Study Group annual meeting ISG2013|
|Periode||27/09/13 → 29/09/13|