Grant: Operating Grant

Insulin secretion from the pancreatic islets of Langerhans is reduced in type 2 diabetes, the most common form of the disease. Much like the way our nerves and muscle cells work, the regular function of insulin-secreting cells is controlled by tiny electrical currents generated by proteins called 'ion channels'. These are often the target of therapeutic drugs such as the sulphonylureas. Our work focuses on a class of ion channels called 'voltage-dependent potassium channels' (Kv channels) which are generally regarded as NEGATIVE-regulators of insulin secretion. We have recently shown however that these channels have a key role in insulin secretion that does not involve their electrical function at all. That is, they play an important POSITIVE role to promote insulin secretion that is independent from their ability to conduct electrical current. Importantly, that these ion channels are severely decreased in islets isolated from human type 2 diabetic patients - this may contribute to reduced insulin secretion in diabetes. This proposal seeks to understand the cellular mechanism by which these ion channels act to promote insulin secretion; whether loss of this contributes to impaired insulin secretion in type 2 diabetes; and the potential of restoring this pathway to rescue insulin secretion in type 2 diabetes.