Grant: Project Grant

High levels of the hormone insulin are a cardinal feature of obesity and early type 2 diabetes, and are induced by unhealthy 'Western diets' high in sugar and fat. It has been suggested that excess insulin contributes to cancer initiation and/or progression, but this has never been tested directly in a way that can address cause and effect. Over the past 5 years, we tested for the first time the hypothesis high levels of insulin play a causal role in pancreatic cancer initiation using new mouse models. Remarkably, our data show a clear reduction in the early stages of pancreatic cancer in the mice that with only a relatively modest reduction in insulin. We now want to know how excess insulin has this cancer promoting effect. Specifically, we want to know whether the effects of insulin are direct on the cancer cells, or indirect by altering something else in the body or the cells that are nearby to the tumours. These studies have the potential to further clarify the known links between insulin and many forms of cancer, as well as uncover the exact mechanisms by which excess insulin influences cancer risk. Our findings will have major implications for both cancer prevention via nutrition/lifestyle modification and for cancer treatment by inhibition of insulin signalling in tumours.