Endocrine Abstracts

Hyperglycaemia in type 2 diabetes is caused by insufficient insulin being secreted by the islet β-cell. In addition, the progressive nature of diabetes is due to the continuing decline of islet β-cell function with time. Currently we do not know what causes islet β-cell dysfunction in diabetes and we do not have effective drugs that specifically target the defect in insulin secretion. Clinical studies show that existing therapies have variable glucose-lowering effects, and a significant proportion of patients with T2D (perhaps up to 50%) have a poor response and therapeutic failure. These responses are likely to have a genetic basis, but currently there is limited information available to predict outcomes. Clearly to provide effective and durable treatment for T2D we first need to identify the genes causing islet β-cell dysfunction and to then understand how drugs can interact with the patient’s genetic constitution. We have been using a powerful genetic resource called the Gene Mine to identify causative genes of type 2 diabetes. We have demonstrated the power, speed and accuracy of our world-leading gene mapping resource in discovery of clinically relevant diabetes genes. By identifying the genes underlying the insulin secretory response and efficacy associated with targeting the incretin response, our findings will assist in identifying and testing new gene targets