Proteome-wide mechanisms of hyperinsulinemia and sucrose-induced, tissue-specific insulin resistance

During the development of Type 2 diabetes, the body often makes more of the blood sugar-lowering hormone insulin than normal. Recent research suggests excess insulin may cause weight gain and insensitivity to insulin. Studies from our lab showed that preventing this increase of insulin can reduce weight gain and extends lifespan in mice. Too much sugar consumption also contributes to obesity and diabetes, but how this happens is still unclear. Therefore, we aim to find out whether reducing insulin can prevent the detrimental effects of high sucrose and identify the underlying causes of obesity and diabetes. So far, our experiments with mice who were given sucrose drink in place of water, have revealed that mice given that have been genetically modified to produce less insulin are protected from higher body weight and blood sugar levels. With funding from Health Research BC, we will analyze the liver, muscle, and fat of these mice using powerful techniques that can profile thousands of genes and proteins in these tissues, rather than just a few at a time. These analyses will reveal the detailed changes in the cells in response to sucrose and insulin, which will tell us how they cause obesity and diabetes and help us develop strategies for preventing diabetes.