ESPE2016 Poster Presentations Perinatal Endocrinology P1 (24 abstracts)
Congenital Hyperinsulinism in Infancy: The Profiles of Insulin Secretory Granules are Markedly Different in Focal- and Diffuse β-Cells
Bing Han a , Zainab Mohamed a, , Maria Salomon-Estebanez a, , Raja Padidela b , Mars Skae b , Ross Craigie b , Lindsey Rigby b , Karen Cosgrove a , Indi Banerjee b & Mark Dunne a
aUniversity of Manchester, Manchester, UK; bChildrens Hospital of Manchester, Manchester, UK
Background: The mechanisms responsible for inappropriate insulin release from β-cells in congenital hyperinsulinism in infancy (CHI) have largely focused upon defects in KATP channels. Little is known about insulin biogenesis, the profiles of insulin in insulin-containing secretory granules or whether the impact of KATP channel defects is the same in diffuse- and focal disease.
Objective and hypotheses: To define the ultrastructural properties of the insulin-containing granules in β-cell different forms of CHI compared to control samples.
Methods: CHI patients were positive for mutations in the KATP channel gene ABCC8 and underwent surgery for the treatment of hypoglycaemia. Morphometric analysis and immuno-gold labelling of insulin (I-Au) was applied to frozen tissue sections of control (n=4) and CHI tissues (diffuse-CHI, n=3; focal-CHI, n=3) and used to identify the insulin-containing granules. Data were acquired using Transmission Electron Microscope from each of the tissue sections; control n=60, diffuse-CHI n=58 and focal-CHI n=61.
Results: Three profiles were defined: mature, dense-core/ crystalline granules; immature secretory granules and secretory granules that were depleted of insulin. Approximately 60% of secretory granules (n=3428) were depleted of insulin in focal-CHI compared to around 10% of granules in diffuse- (n=2258) and control β-cells (n=2577). The percentages of immature granules were significantly lower in focal-CHI (5.7±1.7%) compared with diffuse CHI (45.5±8.7%) and control samples (31.6±3.7%). In contrast, control β-cells had a higher proportions of crystalline granules (62.9±3.1%) compared with focal- (36.6±3.5%) and diffuse-CHI (42.7±1.9%). We also found a higher incidence of multi-vesicular secretory granule structures in focal- (74.7±3.3%) compared to diffuse-CHI and control β-cells (39.5±6.8% vs 27.8±5.6%).
Conclusion: Our data also imply that β-cells in focal-CHI have a greater secretory capacity (increased number multi-vesicular secretory granules and depleted granules) than in diffuse disease, despite the fact that both conditions associate with ABCC8 gene defects.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more