K_ATP channels and insulin secretion: a key role in health and disease

This review summarizes advances in our understanding of the structure and function of the ATP-sensitive potassium (K_ATP) channel of the pancreatic β-cell that have been made over the last 5 years. It discusses recent structural studies of the octameric K_ATP channel complex and studies of the regulation of K_ATP channel activity by nucleotides. It then considers the molecular mechanism by which gain-of-function mutations in the Kir6.2 subunit of the K_ATP channel reduce channel inhibition by ATP and thereby lead to neonatal diabetes, and how identification of these mutations has led to changes in therapy. Finally, it illustrates how mouse models of glucose intolerance or diabetes can provide fresh insight into β-cell function, using the C57BL/6J mouse, whose glucose intolerance arises from mutations in nicotinamide nucleotide transhydrogenase, as an example.