First Author | Zhou L | Year | 2012 |
Journal | PLoS One | Volume | 7 |
Issue | 9 | Pages | e43623 |
PubMed ID | 22970135 | Mgi Jnum | J:191766 |
Mgi Id | MGI:5462522 | Doi | 10.1371/journal.pone.0043623 |
Citation | Zhou L, et al. (2012) Re-expression of IGF-II is important for beta cell regeneration in adult mice. PLoS One 7(9):e43623 |
abstractText | 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-MycER(TAM), 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-MycER(TAM)/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-MycER(TAM)/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. |