The effects of hyperglycemia on glucose metabolism in epithelial ovarian cancer

摘要: THE EFFECTS OF HYPERGLYCEMIA ON GLUCOSE METABOLISM IN EPITHELIAL OVARIAN CANCER Lisa Danielle Kellenberger Advisor: University of Guelph, 2016 Dr. Jim Petrik Glucose metabolism in cancer cells is uniquely adapted to maximize the production both ATP and precursors needed support cell proliferation tissue growth. Glycolysis, an anaerobic process normally limited by presence oxygen, proceeds at elevated rate aerobic conditions. Glycolysis consumes large quantities glucose while producing relatively small amounts energy. The inefficiency this not detrimental when abundant. However, evidence suggests that normal concentration circulating does meet energy demands tumour therefore a limiting factor metabolism. Hyperglycemic conditions such as diabetes are becoming common comorbidities patients associated with increased risk poorer prognosis epithelial ovarian (EOC). We hypothesise blood permits function maximal capacity thereby facilitating growth metastasis. goal thesis was examine metabolic response transport kinetics EOC hyperglycemic environments. By inducing mouse models Type 1 2 diabetes, we found accelerated disease progression occurs concentration-dependent manner. In addition, for first time show express only passive transporters (GLUTs), but also class active transporters, sodium-glucose symporters (SGLTs). uptake into hyperglycemia mediated sodium-dependent transport. Surprisingly, SGLT2 appears be suppressor: knockdown increases relative death tumour-bearing mice more than 50 times. PET scans measuring accumulation analogue fluoro-deoxyglucose (FDG) vital component treatment. FDG poor substrate SGLTs, suggesting current imaging fails detect fraction tumours. use SGLT-specific analogues, particularly dysfunction, presents opportunity enhance power provide complete picture which may have therapeutic benefits.