Direct evidence for new formation of beta cells in the pancreas during the first weeks of life: Neonatal beta cell neogenesis evidenced by lineage tracing

Research output: Unpublished contribution to conferencePoster

Abstract

Background and aims: Diabetes is caused by an insufficient number of insulin-producing beta cells in the pancreas and is a growing public health concern. Stimulation of new beta cell formation and beta cell transplantation offer great hope as diabetes therapies. Yet, these treatments are hindered by a lack of knowledge about the mechanisms of beta cell generation after birth. Several studies indicate that in adult mouse pancreas new beta cells are formed by self-duplication and that there is no evidence for new formation of beta cells from progenitor cells or stem cells in adults. However, new formation of beta cells from non-beta cells might still take place under other conditions e.g. during the first weeks of life (neonatal period). Previously, indirect evidence was reported for new formation of beta cells in this early period of life. More recently, a tracing study suggested generation of beta cells from non-beta cells neonatally. Methods: To quantify new formation of beta cells in the first weeks of life we used genetically engineered mice (RIPCreER Rosa26LoxSTOPLoxYFP). In these mice, beta cells are indelibly genetically labelled by the YFP yellow reporter, only if tamoxifen is administered. In this way the fate of the beta cells can be traced. Pups received tamoxifen on the day of birth and were followed during the next four weeks. Results: From week 1 to week 4, the amount of beta cells present in the pancreas increases a lot. The blood glucose levels remain normal throughout this period both in tamoxifen and non-tamoxifen animals. From week 1 to week 4 after birth, there is a relative decrease in the fraction of small islets (clusters of 1 to 5 beta cells) and a relative increase in the fraction of larger islets (clusters of 11-50 beta cells and >50 beta cells). To quantify new formation of beta cells, tamoxifen-treated mice from week 1 were compared with week 4. Shortly after tamoxifen treatment, beta cells are labelled with a high efficiency and specificity: 84.0 ± 0.4% beta cells are yellow (YFP+) on day 7 after birth. Without tamoxifen, most beta cells remain YFP-. From week 1 to week 4, the percentage of yellow (YFP+) beta cells decreases significantly. The YFP+ fraction of beta cells are beta cells which were already present at birth or originate from self-duplication of beta cells. This indicates that between 1 and 4 weeks of age new beta cells (about 20%) arise from non-beta cells (progenitor cells or stem cells). Both in small and large beta cell clusters (islets) a decrease in YFP+ beta cells is observed. Conclusion: We have obtained direct evidence (via genetic lineage tracing) which confirms that new formation of beta cells from non-beta cells occurs in young mice. Grant Acknowledgement: IH is a research fellow of the Research Foundation - Flanders (FWO)
Original languageEnglish
Publication statusPublished - 17 Dec 2013
EventFWO Anniversary meeting: Kennismakers, al 85 jaar Zuurstof voor Onderzoek en Ontwikkeling - Gent, Belgium
Duration: 17 Dec 2013 → …

Conference

ConferenceFWO Anniversary meeting: Kennismakers, al 85 jaar Zuurstof voor Onderzoek en Ontwikkeling
CountryBelgium
CityGent
Period17/12/13 → …

Fingerprint

Dive into the research topics of 'Direct evidence for new formation of beta cells in the pancreas during the first weeks of life: Neonatal beta cell neogenesis evidenced by lineage tracing'. Together they form a unique fingerprint.

Cite this