ESPE2016 Poster Presentations Perinatal Endocrinology P1 (24 abstracts)
Islet of Langerhans in Congenital Hyperinsulinism in Infancy are Disrupted and with Decreased Expression of Collagen (IV) α1 Chain in Basement Membranes
Walaa Mal a , Maria Salomon-Estebanez a, , Raja Padidela b , Mars Skae b , Ross Craigie b , Lindsey Rigby b , Karen Cosgrove a , Indi Banerjee a & Mark Dunne a
aManchester University, Manchester, UK; bManchester Childrens Hospital, Manchester, UK
Background: Congenital hyperinsulinism of infancy (CHI) is the most common cause of severe hypoglycaemia in children. Although CHI arises from mutations in KATP channels which lead to inappropriate insulin secretion, CHI it also is associated with marked changes in islet organization.
Aims and objectives: Our aim was to investigate the structure and composition of the islet capsule in CHI and age-matched control tissue.
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) tissues and control pancreata with Picro Sirius Red (PSR). Collagen distribution was quantified using a digital macroanalysis after placing the PSR stained slide under polarising microscopy. Then, immunostaining was performed on CHI-D, focal CHI (CHI-F), atypical CHI (CHI-A) and control tissues to examine the expression pattern of collagen (IV) α1 chain (COL4A1) in islets and intra-islet basement membranes.
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≤0.0001) 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).
Summary/conclusion: CHI tissue has disrupted islet architecture and lower collagen content compared to the age-matched control tissues. The decreased expression of COL4A1 supports the involvement of islet matrix in the pathogenesis of CHI.
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