Distribution of glutathione peroxidase-1 immunoreactive cells in pancreatic islets from type 1 diabetic donors and non-diabetic donors with and without islet cell autoantibodies is variable and independent of disease.

Abstract

During type 1 diabetes (T1D), oxidative stress in beta cells may cause early beta cell dysfunction and initiate autoimmunity. Mouse islets express lower levels of reactive oxygen species (ROS) clearing enzymes, such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase than several other tissues. It remains unclear if human beta cells show a similar deficiency during T1D or exhibit a higher degree of intrinsic resistance to oxidative stress. We compared islet cell distributions and determined graded intensities of glutathione peroxidase1 (GPX1), a key enzymatic mediator involved in detoxifying hydrogen peroxide, by applying combined immunohistochemistry for GPX1, insulin and glucagon, in pancreatic sections from new-onset T1D (group 1), non-diabetic autoantibody-negative (group 2), non-diabetic autoantibody-positive (group 3) and long-term diabetic (group 4) donors. Islets from all study groups demonstrated either uniform but graded staining intensities for GPX1 in almost all islet cells or strong staining in selective islet cells with weaker intensities in the remaining cells. GPX1 was present in selective glucagon cells and insulin cells, including in cells negative for both hormones, with stronger intensities in a higher percentage of glucagon than insulin cells. It was absent in a higher percentage of beta cells than glucagon cells independent of disease or autoantibody positivity. We conclude that a proportion of human beta cells and glucagon cells express GPX1 but show heterogeneity in its distribution and intensities, independent of disease or autoantibody status. Our studies highlight important differences in the expression of GPX1 in islet cell-types between mice and humans.