title: Insulin effect on serum potassium and auto-inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism.
abstract: BACKGROUND
  The effect of insulin on glucose, protein metabolism, circulating fatty acids (FFA), potassium (K(+)) and C-peptide concentrations were investigated in a 12-year-old girl with leprechaunism. The mutations do not affect the insulin-receptor binding affinity and insulin-stimulated auto-phosphorylation of the receptor.
  
  
  METHODS
  The subject was studied with a primed-continuous infusion of [6,6 - (2)H(2)] glucose and [1-(13)C] leucine during a basal period followed by two steps of insulin infusion (1 and 10 mU/kg/min) of 2 h each, during which plasma glucose level decreased from 131 to 115 and then to 95 mg/dL.
  
  
  RESULTS
  Whole body glucose disposal was virtually unaffected by insulin, slightly decreasing from 21 micromol/kg/min in the basal period to 20 and to 19 micromol/kg/min during the two steps of insulin infusion, respectively. The endogenous leucine flux, an index of proteolysis, was completely insensitive to insulin, being 182, 189 and 180 micromol/kg/min, in the three periods, respectively. The FFA concentration (an indirect index of lipolysis) decreased from 1135 to 799 during step 1. During step 2 the FFA concentration rebounded to 917 micromol/L. The concentration of K(+) decreased from 4.2 to 3.2 mmol/L and an infusion of 20 mEq/h of KCl was necessary to prevent further hypokalemia (final value 3.3 mmol/l). The C-peptide concentration declined from 1.85 to 0.97 and then to 0.29 pmol/mL.
  
  
  CONCLUSIONS
  The dissociation of control exerted by insulin on K+ uptake and on beta-cell secretion may rely on a differential expression and folding of the mutated receptors in the different insulin target tissues.
authors.affiliation: Department of Medicine, San Raffaele Scientific Institute, and University of Milano, Milano, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Luzi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Zoppini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Targher
authors.forename: Alberto
authors.initials: A
authors.lastname: Battezzati
authors.forename: Michele
authors.initials: M
authors.lastname: Muggeo
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
mesh_terms: D000015:Abnormalities, Multiple / Q000097:blood / Q000503:physiopathology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology*; D000078790:Insulin Secretion; D007930:Leucine / Q000008:administration & dosage / Q000378:metabolism; D011188:Potassium / Q000097:blood*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D007930:Leucine; D005947:Glucose; D011188:Potassium