Atypical Forms of Congenital Hyperinsulinism in Infancy Are Associated With Mosaic Patterns of Immature Islet Cells.
J Clin Endocrinol Metab
; 102(9): 3261-3267, 2017 09 01.
Article
em En
| MEDLINE
| ID: mdl-28605545
ABSTRACT
Objectives:
We aimed to characterize mosaic populations of pancreatic islet cells from patients with atypical congenital hyperinsulinism in infancy (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in ß-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods:
Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal and diffuse CHI (CHI-D). Immunohistochemistry was used to identify and quantify the proportions of insulin-secreting ß-cells and somatostatin-secreting δ-cells in atypical islets, and results were compared with CHI-D (n = 3) and age-matched control tissues (n = 3).Results:
In CHI-A tissue, islets had a heterogeneous profile. In resting/quiescent islets, identified by a condensed cytoplasm and nuclear crowding, ß-cells were reduced to <50% of the total cell numbers in n = 65/70 islets, whereas δ-cell numbers were increased with 85% of islets (n = 49/57) containing >20% δ-cells. In comparison, all islets in control tissue (n = 72) and 99% of CHI-D islets (n = 72) were composed of >50% ß-cells, and >20% δ-cells were found only in 12% of CHI-D (n = 8/66) and 5% of control islets (n = 3/60). Active islets in CHI-A tissue contained proportions of ß-cells and δ-cells similar to those of control and CHI-D islets. Finally, when compared with active islets, quiescent islets had a twofold higher prevalence of somatostatin/NKX2.2+ coexpressed cells.Conclusions:
Marked increases in NKX2.2 expression combined with increased numbers of δ-cells strongly imply that an immature δ-cell profile contributed to the pathobiology of CHI-A.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Nucleares
/
Ilhotas Pancreáticas
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Predisposição Genética para Doença
/
Hiperinsulinismo Congênito
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article