Altered Phenotype of ß-Cells and Other Pancreatic Cell Lineages in Patients With Diffuse Congenital Hyperinsulinism in Infancy Caused by Mutations in the ATP-Sensitive K-Channel.
Diabetes
; 64(9): 3182-8, 2015 Sep.
Article
em En
| MEDLINE
| ID: mdl-25931474
ABSTRACT
Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel; however, the phenotype is difficult to explain from electrophysiology alone. Here we studied wider abnormalities in the ß-cell and other pancreatic lineages. Islets were disorganized in CHI-D compared with controls. PAX4 and ARX expression was decreased. A tendency toward increased NKX2.2 expression was consistent with its detection in two-thirds of CHI-D δ-cell nuclei, similar to the fetal pancreas, and implied immature δ-cell function. CHI-D δ-cells also comprised 10% of cells displaying nucleomegaly. In CHI-D, increased proliferation was most elevated in duct (5- to 11-fold) and acinar (7- to 47-fold) lineages. Increased ß-cell proliferation observed in some cases was offset by an increase in apoptosis; this is in keeping with no difference in INSULIN expression or surface area stained for insulin between CHI-D and control pancreas. However, nuclear localization of CDK6 and P27 was markedly enhanced in CHI-D ß-cells compared with cytoplasmic localization in control cells. These combined data support normal ß-cell mass in CHI-D, but with G1/S molecules positioned in favor of cell cycle progression. New molecular abnormalities in δ-cells and marked proliferative increases in other pancreatic lineages indicate CHI-D is not solely a ß-cell disorder.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Secretoras de Somatostatina
/
Hiperinsulinismo Congênito
/
Células Secretoras de Glucagon
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Células Secretoras de Insulina
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
Limite:
Child
/
Child, preschool
/
Humans
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Infant
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Newborn
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article