title: Protein-sensitive hypoglycemia without leucine sensitivity in hyperinsulinism caused by K(ATP) channel mutations.
abstract: OBJECTIVE
  Because children with congenital hyperinsulinism (HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel (K(ATP)-HI) are not leucine sensitive, we evaluated for protein-induced hypoglycemia with oral protein tolerance tests.
  
  
  METHODS
  Blood glucose and insulin concentrations were measured every 15 minutes for 3 hours after an oral protein load in children with K(ATP)-HI (n = 11) and compared with those of children with glutamate dehydrogenase HI (n = 12) and control subjects (n = 12).
  
  
  RESULTS
  Similar to children with glutamate dehydrogenase HI, patients with K(ATP)-HI displayed protein-induced hypoglycemia (10/11) with blood glucose concentrations declining by 17 to 69 mg/dL. In contrast, oral protein had little effect on blood glucose concentrations in control subjects.
  
  
  CONCLUSIONS
  Protein-induced hypoglycemia is a feature of K(ATP)-HI, despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretion via a glutamate dehydrogenase- and K(ATP) channel-independent pathway.
authors.affiliation: Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Shannon H
authors.initials: SH
authors.lastname: Fourtner
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stanley
authors.forename: Andrea
authors.initials: A
authors.lastname: Kelly
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D044903:Congenital Hyperinsulinism / Q000235:genetics*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology* / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood; D007930:Leucine; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000009:adverse effects*; D011955:Receptors, Drug / Q000235:genetics* / Q000378:metabolism; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D005969:Glutamate Dehydrogenase; D007930:Leucine