Channelpedia

PubMed 25931474


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir2.3 , Kv10.1



Title: Altered Phenotype of β-Cells and Other Pancreatic Cell Lineages in Patients With Diffuse Congenital Hyperinsulinism in Infancy Caused by Mutations in the ATP-Sensitive K-Channel.

Authors: Rachel J Salisbury, Bing Han, Rachel E Jennings, Andrew A Berry, Adam Stevens, Zainab Mohamed, Sarah A Sugden, Ronald De Krijger, Sarah E Cross, Paul P V Johnson, Melanie Newbould, Karen E Cosgrove, Karen Piper Hanley, Indraneel Banerjee, Mark J Dunne, Neil A Hanley

Journal, date & volume: Diabetes, 2015 Sep , 64, 3182-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/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 β-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 β-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 β-cells compared with cytoplasmic localization in control cells. These combined data support normal β-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 β-cell disorder.