Insulin effect on serum potassium and auto-inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism

Livio Luzi, Giacomo Zoppini, Giovanni Targher, Alberto Battezzati, Michele Muggeo, Enzo Bonora

Research output: Contribution to journalArticle

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 [6,6-2H2] glucose and [1-13C] 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 μmol/kg/min in the basal period to 20 and to 19 μmol/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 μmol/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 μmol/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/1). 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 β-cell secretion may rely on a differential expression and folding of the mutated receptors in the different insulin target tissues.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalDiabetes/Metabolism Research and Reviews
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2008

Fingerprint

Donohue Syndrome
Metabolism
Potassium
Insulin
Substrates
Serum
Glucose
C-Peptide
Leucine
Proteolysis
Phosphorylation
Hypokalemia
Lipolysis
Insulin Receptor
Fatty Acids
Tissue
Fluxes

Keywords

  • Free fatty acid
  • Glucose metabolism
  • Insulin resistance
  • Leprechaunism
  • Potassium and C-peptide
  • Protein metabolism

ASJC Scopus subject areas

  • Endocrinology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Insulin effect on serum potassium and auto-inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism. / Luzi, Livio; Zoppini, Giacomo; Targher, Giovanni; Battezzati, Alberto; Muggeo, Michele; Bonora, Enzo.

In: Diabetes/Metabolism Research and Reviews, Vol. 24, No. 3, 03.2008, p. 205-210.

Research output: Contribution to journalArticle

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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 [6,6-2H2] glucose and [1-13C] 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 μmol/kg/min in the basal period to 20 and to 19 μmol/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 μmol/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 μmol/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/1). 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 β-cell secretion may rely on a differential expression and folding of the mutated receptors in the different insulin target tissues.",
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T1 - Insulin effect on serum potassium and auto-inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism

AU - Luzi, Livio

AU - Zoppini, Giacomo

AU - Targher, Giovanni

AU - Battezzati, Alberto

AU - Muggeo, Michele

AU - Bonora, Enzo

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N2 - 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 [6,6-2H2] glucose and [1-13C] 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 μmol/kg/min in the basal period to 20 and to 19 μmol/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 μmol/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 μmol/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/1). 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 β-cell secretion may rely on a differential expression and folding of the mutated receptors in the different insulin target tissues.

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