Mouse Models of β-cell K_ATP Channel Dysfunction

ATP-sensitive K⁺ (K_ATP) channels in pancreatic β-cells couple glucose metabolism to insulin secretion. Reduced K_ATP channel activity produces excessive insulin release and hyperinsulinism whereas increased K_ATP channel activity leads to lower insulin secretion and diabetes. Paradoxically, mice with genetic deletion of K_ATP channels, or loss-of-function mutations, are only transiently hypoglycaemic during the neonatal period and often display reduced glucose-stimulated insulin secretion subsequently. Mice with K_ATP channel gain-of-function mutations are hyperglycaemic and have impaired glucose-stimulated insulin secretion, a phenotype that accurately mimics human diabetes. This review discusses how mice expressing altered K_ATP channels have provided valuable insight into β-cell function.