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

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.