Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy.
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 (KATP) activity. As a consequence, PHHI beta-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.
Kane
C
C
Department of Biomedical Science, University of Sheffield, UK.
Shepherd
R M
RM
Squires
P E
PE
Johnson
P R
PR
James
R F
RF
Milla
P J
PJ
Aynsley-Green
A
A
Lindley
K J
KJ
Dunne
M J
MJ
D018528:ATP-Binding Cassette Transporters; D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism*; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014700:Verapamil / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D014700:Verapamil