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Re-expression of IGF-II is important for beta cell regeneration in adult mice
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Zhou, Luxian, Pelengaris, Stella, Abouna, Sylvie, Young, James, Epstein, D. B. A., Herold, Julia, Nattkemper, Tim W., Nakhai, Hassan and Khan, Michael (2012) Re-expression of IGF-II is important for beta cell regeneration in adult mice. PLoS ONE, Vol.7 (No.9). e43623. doi:10.1371/journal.pone.0043623 ISSN 1932-6203.
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Official URL: http://dx.doi.org/10.1371/journal.pone.0043623
Abstract
Background
The key factors which support re-expansion of beta cell numbers after injury are largely unknown. Insulin-like growth factor II (IGF-II) plays a critical role in supporting cell division and differentiation during ontogeny but its role in the adult is not known. In this study we investigated the effect of IGF-II on beta cell regeneration.
Methodology/Principal Findings
We employed an in vivo model of ‘switchable’ c-Myc-induced beta cell ablation, pIns-c-MycERTAM, in which 90% of beta cells are lost following 11 days of c-Myc (Myc) activation in vivo. Importantly, such ablation is normally followed by beta cell regeneration once Myc is deactivated, enabling functional studies of beta cell regeneration in vivo. IGF-II was shown to be re-expressed in the adult pancreas of pIns-c-MycERTAM/IGF-II+/+ (MIG) mice, following beta cell injury. As expected in the presence of IGF-II beta cell mass and numbers recover rapidly after ablation. In contrast, in pIns-c-MycERTAM/IGF-II+/− (MIGKO) mice, which express no IGF-II, recovery of beta cell mass and numbers were delayed and impaired. Despite failure of beta cell number increase, MIGKO mice recovered from hyperglycaemia, although this was delayed.
Conclusions/Significance
Our results demonstrate that beta cell regeneration in adult mice depends on re-expression of IGF-II, and supports the utility of using such ablation-recovery models for identifying other potential factors critical for underpinning successful beta cell regeneration in vivo. The potential therapeutic benefits of manipulating the IGF-II signaling systems merit further exploration.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QL Zoology | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Pancreatic beta cells -- Regeneration, Somatomedin, Mice -- Physiology | ||||
| Journal or Publication Title: | PLoS ONE | ||||
| Publisher: | PLOS | ||||
| ISSN: | 1932-6203 | ||||
| Official Date: | 2012 | ||||
| Dates: |
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| Volume: | Vol.7 | ||||
| Number: | No.9 | ||||
| Page Range: | e43623 | ||||
| DOI: | 10.1371/journal.pone.0043623 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||
| Date of first compliant deposit: | 22 December 2015 | ||||
| Date of first compliant Open Access: | 22 December 2015 | ||||
| Funder: | University of Warwick, Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University of Warwick. Medical And Life Sciences Research Fund |
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