Short term effects of c-MYC activation on β-cell physiology and glucose homeostasis in the pIns-c-MycERTAM transgenic mouse

• Main Author: Wang, Yi-Fang
• Published: University of Warwick 2012
• Subjects: 571.1; QL Zoology
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.560310

Injection of 4-hydroxytamoxifen (4-OHT) activates the oncogene c-myc in transgenic pIns-c-MycERTAM mice, triggering β-cell proliferation in the short term as well as apoptosis and reduced insulin secretion, leading to hyperglycaemia. This hyperglycaemia is preceded by a short period of hypoglycaemia, which may be caused by: (i) increased insulin secretion or release from dying cells; (ii) rapid β-cell proliferation; and (iii) increased insulin sensitivity. This thesis characterizes the initial stages of the expression of c-MYC in the plns-c-MycERTAM mouse model and attempts to identify the causes of the transient hypoglycaemia using mathematical models. Furthermore, microarray data were analysed to investigate the early hypoglycaemia from the point of view of transcriptomics. The size and mass of β-cells were quantified during the transient period of hypoglycaemia by means of immunohistochemistry. These data were incorporated in a detailed mathematical model of β-cell dynamics.