Oxidative modification, inflammation and amyloid in the normal and diabetic cat pancreas.

The pathogenesis of β-cell dysfunction leading to pancreatic β-cell failure seen in type 2 diabetes mellitus is incompletely understood. Pancreatic tissues were collected from nine control cats and nine diabetic cats and labelled immunohistochemically to examine expression of interleukin (IL)-1β, insulin, islet amyloid polypeptide (IAPP) and 4-hydroxynonenal (4-HNE). Thioflavin-S was used to stain for amyloid. All control cats showed positive labelling for IL-1β and 4-HNE. Diabetic cats showed varying degrees of inflammation and oxidative modification, owing in large part to the very small amount of islet structure remaining in the typical diabetic cat pancreas. Amyloid deposition was identified in 8/9 diabetic cats and 1/9 control cats. In order to validate these findings, paired biopsy samples taken from an additional group of cats enrolled in a study of obesity and hyperglycaemia (sampling at baseline and after 8-16 weeks of obesity and hyperglycaemia) were labelled for IL-1β and 4-HNE. A similar pattern of labelling was identified in the baseline samples to that seen in control cats. A significant increase in IL-1β and 4-HNE expression was seen after a period of hyperglycaemia and obesity. Taken together, these findings suggest that while present in normal cats, markers of inflammation and oxidative modification increase very early during the development of disease. Future studies focusing on these earlier time points are needed to understand the factors that function in protection of the islet β cell and the development of islet pathology in type 2 diabetes mellitus in the cat.