Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism.
J Clin Endocrinol Metab
; 87(10): 4502-7, 2002 Oct.
Article
en En
| MEDLINE
| ID: mdl-12364426
Mutations in genes encoding the two subunits of the beta-cell ATP-sensitive potassium channel (K(ATP)) channel (SUR1 and Kir6.2) are the major cause of congenital hyperinsulinism (CHI). In this study, the K(ATP) channel genes were screened in a population-based study that included all verified Finnish CHI patients (n = 43) in a 27-yr period. Seven different mutations were identified, which accounted for 60% of all cases. The functional consequences of the major missense mutations were studied in vivo by determining acute (1-3 min) plasma insulin and C-peptide responses to calcium (n = 18), glucose (n = 12), and tolbutamide (n = 11) in those CHI patients who were able to take part in these studies. C-peptide and insulin responses to calcium were significantly higher in the patients with SUR1-E1506K mutation, compared with patients without K(ATP) channel mutations. The patients with SUR1-V187D mutation showed a reduced response to tolbutamide but unexpectedly did not show any response to calcium stimulation. A compound heterozygous patient with Kir6.2-(-54)/K67N mutations responded to calcium but also to tolbutamide. In conclusion, our results show that a positive response in the calcium test is indicative of a K(ATP) channel mutation, but all mutations cannot be identified with this method. The insulin response to tolbutamide in patients with SUR1 mutations is impaired to different extents, depending on the genotype. The combination of calcium and tolbutamide tests is a useful tool for the detection of CHI patients with K(ATP) channel dysfunction. Our results, however, also demonstrate the complexity of these responses and the difficulties in their interpretation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Saccharomyces cerevisiae
/
Hiperinsulinismo
/
Insulina
/
Proteínas de la Membrana
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adolescent
/
Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2002
Tipo del documento:
Article
País de afiliación:
Finlandia
Pais de publicación:
Estados Unidos