Insulin expression in β cells is reduced within islets before islet loss in diabetic cats by Valeria Bergomi and colleagues at the University of Cambridge
In 2019, Dr Kate Hughes at the University of Cambridge was awarded PetSavers funding for a master’s project to investigate the islet microenvironment as an unexplored therapeutic target for canine and feline diabetes. Her student Valeria Bergomi is first author on a paper published in the November 2022 issue of the Journal of Small Animal Practice (JSAP) describing pathological changes associated with diabetes mellitus (DM) in feline pancreatic islets.
DM is a common endocrinopathy of cats that often requires intensive and lifelong interventions. This study used immunohistochemistry and immunofluorescence of formalin-fixed paraffin-embedded tissues to compare the islet microenvironment between 9 DM cats and 10 with no clinical history of DM, and also explored the use of clear, unobstructed, brain imaging cocktail and computational analysis (CUBIC) imaging technology to allow a deep 3D visualisation of microscopic structures.
The study revealed a significantly reduced overall islet mass in diabetic cats (standard error=0.0389, t value=−4.490, P=0.0003) and significantly lower insulin expression from β cells prior to cell loss compared with control cats (standard error=0.1295, t value=−2.827, P=0.0121).
CUBIC can be used to optically clear formalin-fixed tissue, and in this study was combined with immunofluorescence to label pancreatic islets. The optimisation of this technique allowed a highly detailed assessment of the islet shape to be achieved, suggesting it will prove a powerful future tool to investigate the 3D islet microanatomy of cats.
These findings support the theory that a decrease in the function of β cells occurs before their destruction in DM cats, as shown by the reduction in insulin expression, which may reflect a feline equivalent to the human DM stage between prediabetes and the irreversible loss of islets. The identification and characterisation of islet function loss could provide the basis for earlier testing and/or intervention of DM in cats.
Immunofluorescence for insulin (gold), synaptophysin (synapto; magenta) and DNA (DAPI; cyan) in non‐diabetic (A) and diabetic (B) feline pancreas. Scale bar = 50 μm. Images are representative of 18 biological repeats. J of Small Animal Practice, First published: 19 August 2022, DOI: (10.1111/jsap.13541)