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Can beta cells regenerate following severe injury when only few pre-existing beta cells are left and what other cell types are involved? We have studied mice that remain permanently diabetic after alloxan unless they are treated with miniosmotic pumps delivering two growth or differentiation factors, namely either EGF (epidermal growth factor) and gastrin or EGF and CNTF (ciliary neurotrophic factor). These treatments resulted in partial or total restoration of normoglycenmia and this was associated with partial recovery of the beta cell mass. After both treatments, genetic lineage tracing with RIP-CreERT mice demonstrated ilution of labelled beta cells, thus indicating that neogenesis contributed to the beta cell regeneration. To find out whether Ngn3+ progenitor/precursor cells were involved in the neogenesis, expression of Ngn3 was analyzed. Whereas the treatment with CNTF/EGF induced upregulation of Ngn3 mRNA and augmented the number of Ngn3-expressing cells, treatment with gastrin/EGF did not have this effect. Most of the Ngn3-expressing cells following EGF/CNTF were acinar cells. Genetic lineage tracing with Elastase-CreERT mice confirmed that some of the beta cells were derived from acinar cells after CNTF/EGF but not after gastrin/EGF treatment. In the latter model we previously demonstrated that duct cells do not contribute to beta cell regeneration. We conclude that there is a context-dependency of the mechanisms involved in beta cell regeneration. Our observations demonstrate that acinar cells contribute to beta cell neogenesis after EGF/CNTF treatment but that (an)other cell type(s), still to be identified, can contribute to beta cell neogenesis following EGF/gastrin treatment.
|Titel||Oral presentation at BetaCell Workshop 2011: Programming beta cell development, impairment and regeneration, Helsingor, Denmark|
|Status||Published - 23 okt 2011|
|Evenement||Unknown - |
Duur: 23 okt 2011 → …
|Periode||23/10/11 → …|
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