BSPED2016 Poster Presentations Miscellaneous/other (14 abstracts)
Altered islet architecture in congenital hyperinsulinism in infancy
Walaa Mal 1 , Maria Salomon-Estebanez 1, , Bing Han 1 , Raja Padidela 2 , Mars Skae 2 , Ross Craigie 2 , Karen Cosgrove 1 , Indi Banerjee 2 & Mark Dunne 1
1University of Manchester, Manchester, UK; 2Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Background: Congenital hyperinsulinism of infancy (CHI) is the most common cause of severe hypoglycaemia in children. CHI arises from mutations in ion channel genes (ABCC8/KCNJ11), which lead to inappropriate insulin secretion. CHI is also associated with increased cell proliferation and altered islet cell development. The aim of this study was to investigate the composition of the islet capsule in CHI and to relate this to the organisation of islet cells.
Methods: Pancreata were obtained from CHI patients following surgery and from autopsy specimens of age-matched control infants. Islet capsule and intra-islet blood vessels structures were demonstrated after staining diffuse CHI (CHI-D) and control pancreata with PicroSirius Red (PSR). Collagen distribution was quantified using a digital macroanalysis after placing the PSR stained slides under polarising microscopy. Immunostaining was performed to examine the expression pattern of collagen (IV) α1 chain (COL4A1) in islets and intra-islet basement membranes.Confocal microscopy was used to examine the relationship between COL4A1 and glucagon-secreting α-cells.
Results: PSR staining showed that control islets are surrounded by defined layer of basement membrane (BM). In CHI-D (n=7, 2–13 months), 75% of islets were incompletely encapsulated compared to only 22% in control islets (n=4, age 7 weeks-10 months). When collagen content was quantified, CHI-D was significantly lower (P<0.001) than control islets and this was found to be associated with a marked decrease in the expression of COL4A1in CHI-D (n=4, 2–5 months). Three dimensional imaging using confocal microscopy of CHI-D (n=2, 5 months) islets revealed that α-cells were largely dissociated from the islet capsule and capillaries when compared to age-matched controls.
Summary/Conclusion: CHI tissue has disrupted islet architecture including a lower collagen content compared to the age-matched control tissues, and the disassociation of glucagon producing α-cells from the basement membrane. The decreased expression of COL4A1 supports the involvement of islet matrix in the pathogenesis of CHI.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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