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Insulin expression in β cells is reduced prior to islet loss in diabetic cats

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Bergomi, Valeria 
Beck, Samuel 
Dobromylskyj, Melanie 
Davison, Lucy 
Wills, John 


Objectives Diabetes mellitus (DM) is a common condition that requires intensive treatment and markedly impacts the welfare of affected cats. The aim of this study was to identify DM-associated perturbations in the feline pancreatic islet microenvironment. The utility of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) for three-dimensional (3D) pancreatic analysis was investigated.

Methods Formalin fixed paraffin embedded tissues from cats with DM, or control cats without pancreatic pathology, were retrospectively identified. Immunohistochemistry for synaptophysin and ionised calcium binding adaptor molecule 1 (IBA1), and immunofluorescence for insulin and synaptophysin, were used to assess changes in islets. An image analysis pipeline was developed to analyse images acquired from two-dimensional immunofluorescence. CUBIC was used to optically clear selected pancreas samples prior to immunofluorescence and deep 3D confocal microscopy.

Results Diabetic cats have a significant reduction in synaptophysin-positive islet area. Whilst islets from diabetic patients have similar numbers of β cells to islets from control cats, significantly lower intensity of insulin expression can be observed in the former. CUBIC facilitates clear visualisation of pancreatic islets in 3D.

Clinical significance The data presented support the theory that there is a decrease in function of β cells prior to their destruction, suggesting a potentially significant step in the pathogenesis of feline DM. In parallel, we demonstrate CUBIC technology as a valuable new tool to visualise the shape of feline pancreatic islets and to interrogate pathology occurring in the islets of diabetic pets.



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Journal of Small Animal Practice

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PetSavers (MDR 04.19)
BSAVA PetSavers reference MDR 04.19