Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice

Zhou L, Pelengaris S, Abouna S, Young J, Epstein D, Herold J, Nattkemper TW, Nakhai H, Khan M (2012)
PLoS ONE 7(9): e43623.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Zhou, Luxian; Pelengaris, Stella; Abouna, Sylvie; Young, James; Epstein, David; Herold, JuliaUniBi; Nattkemper, Tim WilhelmUniBi ; Nakhai, Hassan; Khan, Michael
Abstract / Bemerkung
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-cMycER(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.
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Zhou L, Pelengaris S, Abouna S, et al. Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice. PLoS ONE. 2012;7(9): e43623.
Zhou, L., Pelengaris, S., Abouna, S., Young, J., Epstein, D., Herold, J., Nattkemper, T. W., et al. (2012). Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice. PLoS ONE, 7(9), e43623. doi:10.1371/journal.pone.0043623
Zhou, L., Pelengaris, S., Abouna, S., Young, J., Epstein, D., Herold, J., Nattkemper, T. W., Nakhai, H., and Khan, M. (2012). Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice. PLoS ONE 7:e43623.
Zhou, L., et al., 2012. Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice. PLoS ONE, 7(9): e43623.
L. Zhou, et al., “Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice”, PLoS ONE, vol. 7, 2012, : e43623.
Zhou, L., Pelengaris, S., Abouna, S., Young, J., Epstein, D., Herold, J., Nattkemper, T.W., Nakhai, H., Khan, M.: Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice. PLoS ONE. 7, : e43623 (2012).
Zhou, Luxian, Pelengaris, Stella, Abouna, Sylvie, Young, James, Epstein, David, Herold, Julia, Nattkemper, Tim Wilhelm, Nakhai, Hassan, and Khan, Michael. “Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice”. PLoS ONE 7.9 (2012): e43623.

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