Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters*
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Action Potentials
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Adenosine Triphosphate / physiology*
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Calcium Channel Blockers / pharmacology
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Cells, Cultured
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Humans
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Hyperinsulinism / metabolism*
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Hypoglycemia / blood
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Hypoglycemia / metabolism*
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Infant, Newborn
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Islets of Langerhans / physiology*
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Potassium Channels / metabolism*
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Potassium Channels, Inwardly Rectifying*
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Receptors, Drug
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Sulfonylurea Receptors
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Verapamil / pharmacology
Substances
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ATP-Binding Cassette Transporters
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Calcium Channel Blockers
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Receptors, Drug
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Sulfonylurea Receptors
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Adenosine Triphosphate
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Verapamil