Loss of functional K(ATP) channels in pancreatic β-cells causes persistent hyperinsulinemic hypoglycemia of infancy
Kane C., Shepherd RM., Squires PE., Johnson PRV., James RFL., Milla PJ., Aynsley-Green A., Lindley KJ., Dunne MJ.
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder of childhood associated with inappropriate hypersecretion of insulin by the pancreas. The pathogenesis of the condition has hitherto remained controversial. We show here that insulin-secreting cells from a homogeneous group of five infants with PHHI lack ATP-sensitive K+ channel (K(ATP)) activity. As a consequence, PHHI β-cells are spontaneously electrically active with high basal cytosolic Ca2+ concentrations due to Ca2+ influx. Our findings define the pathogenesis of this disease as a novel K+ channel disorder.