Frances Ashcroft's research aims to understand how glucose regulates insulin secretion from the pancreatic islets of Langerhans and how this process is impaired in disease. Around 25 years ago she discovered that the ATP-sensitive potassium (KATP) channel serves as the molecular link between glucose metabolism and insulin secretion from pancreatic beta-cells. Closing of this channel in response to metabolically generated ATP (or antidiabetic sulphonylurea drugs) stimulates insulin secretion.
Ashcroft's more recent collaborative studies have shown that mutations in the genes that encode KATP channel subunits cause neonatal diabetes by impairing the ability of ATP to close the channel. In most cases, however, sulphonylurea inhibition is not affected, enabling patients to switch from insulin injections to drug therapy. Her current studies continue to focus on the KATP channel, and range from attempts to define its atomic structure to understanding the molecular basis of the neurological complications found in some human patients with KATP channel mutations.