Abstract
The putative induction of adult b-cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel b-cell ablation mouse model, in which the b-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the b-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IAD/D). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted b-cell death. In this model, we observed b-cell regeneration that resulted in a complete recovery of the b-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining b-cells is the prominent mechanism acting to compensate for the massive b-cell loss in young but also aged mice. Interestingly, at any age, we also detected b-like cells expressing the glucagon hormone, suggesting a transition between a- and b-cell identities or vice versa. Taken together, the TIF-IAD/D mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting b-cell regeneration.
Original language | English (US) |
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Pages (from-to) | 3948-3957 |
Number of pages | 10 |
Journal | Cell Cycle |
Volume | 13 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2014 |
Keywords
- B-cell proliferation
- Diabetes
- Insulin
- Islet of langerhans
- Pancreatic b-cell
- Regeneration
- TIF-IA
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology