Zhou, Luxian (2010) Functional study of beta cell mass regulation in vivo. PhD thesis, University of Warwick.

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Abstract

Those key factors, supporting re-expansion of beta cell numbers after injury in
various model systems, are largely unknown. Insulin-like growth factor II
(IGF-II), an important member from the IGF family, 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 in beta
cell regeneration. An in vivo model of „switchable‟ c-Myc-induced beta cell
ablation, pIns-c-MycERTAM (Pelengaris, Khan et al. 2002), which exhibits beta
cell regeneration once Myc is deactivated, is employed in this study of the
IGF-II function. Here we show for the first time that IGF-II is re-expressed in
the adult pancreas following beta cell injury. Moreover, whereas a 90% beta
cell ablation was induced in both pIns-cMycERTAM/IGF-II WT (MIG) and
pIns-cMycERTAM/IGF-II KO (MIGKO) mice, a recovery up to 3 months was
performed. By investigating the beta cell mass and numbers our results
demonstrate that re-expression of IGF-II is important in supporting the beta
cell regeneration in adult mice. Moreover this study supports the utility of
using such ablation-recovery models for identifying other potential factors
critical for underpinning successful beta cell regeneration in vivo.
Both Myc and PML contribute to the regulation of apoptosis. Recent studies
suggest that Myc and PML may interact at several levels in control of cell fate. Here we examined whether loss of the PML protein, which has been shown to
regulate apoptosis via the p53 pathway, can prevent or affect c-Myc-induced
beta cell apoptosis in pIns-c-MycERTAM transgenic mice.
Together with the Applied Neuroinformatics Group at the University of
Bielefeld in Germany, we have been developing and validating a machine
learning based system to analyze beta and alpha cell numbers (Herold, Zhou et
al. 2009). Comparative results between traditional techniques and this new
method are presented here.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Pancreatic beta cells -- Regeneration, Somatomedin, Apoptosis
Official Date:	September 2010
Dates:	Date Event September 2010 Submitted
Institution:	University of Warwick
Theses Department:	Department of Biological Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Khan, Michael ; Pelengaris, Stella
Sponsors:	University of Warwick
Extent:	xvi, 196 leaves : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/34648

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