The potential role of copper in type 2 diabetes mellitus
Supervisor: Professor David Allsop
The formation of amyloid fibrils from a variety of different proteins is a common link between many apparently unrelated diseases. One of these diseases is type 2 diabetes mellitus (T2DM), which is associated with older age, obesity and physical inactivity, but is increasingly being diagnosed in children and adolescents. More than 90% of patients with T2DM go on to develop amyloid deposits in the islets of Langerhans of the pancreas and these are formed from a peptide called 'islet amyloid polypeptide' or 'amylin'. When T2DM is first diagnosed, the pancreas is usually producing enough insulin, but the body cannot use it effectively. After several years, however, insulin production decreases, due at least in part to the loss of islet beta-cells. The formation of amyloid deposits in the pancreas is thought to be a significant factor in islet cell degeneration.
This project will focus on one potential mechanism for the cellular toxicity of amylin, namely its ability to generate reactive oxygen species (ROS) as it aggregates into amyloid fibrils. We have discovered (see reference) that, in vitro, amylin has the ability to generate hydrogen peroxide and hydroxyl free radicals, and that this process is greatly stimulated by copper ions. The levels of copper are increased in blood from diabetic patients. This project will focus on the role of copper ions on amylin aggregation, the associated generation of ROS, and amylin toxicity towards islet cells grown in culture.