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Title: The organization and structure of islets of Langerhans in Congenital Hyperinsulinism in Infancy
Author: Mal, Walaa
ISNI:       0000 0004 8504 9259
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2019
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Congenital Hyperinsulinism in Infancy (CHI) is a potentially lethal disease that leads to severe hypoglycaemia in children due to the impaired insulin release by β-cells. The disease is genetically and histologically heterogeneous; however, a complete understanding of the islet organization and structure in CHI is lacking. We hypothesized that the altered cellular organization and the altered matrix composition may contribute to CHI pathology. In this thesis, the histopathology of the islet of Langerhans was investigated from different aspects: identifying the islet architecture in diffuse CHI (CHI-D), focal CHI (CHI-F) and control tissues in a 2-dimensional level, understanding the different endocrine cell organizational patterns within islets from CHI-D, CHI-F and control tissues in a 3- dimensional level, and assessing the expression patterns of several proteins found in the islet of Langerhans from CHI-D, CHI-F and control tissues. Transmission electron microscopy (TEM) was also introduced in this study to provide high-resolution images of endocrine cells from CHI-tissues. By assessing the islet architecture using histochemical staining, islets from control tissues were round- to- oval microstructures that were embedded within the exocrine tissue and separated from it by a capsule and islets were enriched with capillaries. Interestingly, different encapsulation patterns were observed in CHI disease. Incomplete encapsulation was observed in islets from CHI-D and some of these islets were hypervascularized. In CHI-F disease, the findings showed that within the non-lesion domains, islets were normally encapsulated. However, the lesion parts showed islet-like units that were highly enriched with capillaries. By assessing the endocrine cell organization, α-, β- and δ-cells were disorganized within the CHI islets. Significant changes were detected in collagen IV, vascular endothelial growth factor-A and thrombospondin-1. These data expanded our knowledge on understanding CHI disease and provided us with new clues that the endocrine cellular organization with islet matrix and blood vessels is important for normal islet function.
Supervisor: Dunne, Mark ; Hanley, Neil Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Collagen IV ; Blood vessels ; laminin 511 ; Islet basement membranes ; Focal Congenital Hyperinsulinism ; Diffuse Congenital Hyperinsulinism ; Islet organization ; Congenital Hyperinsulinism ; Islets