Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINS^C94Ytransgenic pigs

Abstract

People with diabetes mellitus have an increased risk for infections, however, there is still a critical gap in precise knowledge about altered immune mechanisms in this disease. Since diabetic INSC94Y transgenic pigs exhibit elevated blood glucose and a stable diabetic phenotype soon after birth, they provide a favourable model to explore functional alterations of immune cells in an early stage of diabetes mellitus in vivo. Hence, we investigated peripheral blood mononuclear cells (PBMC) of these pigs compared to non-transgenic wild-type littermates. We found a 5-fold decreased proliferative response of T cells, disturbed by chronic hyperglycaemia, to polyclonal T cell mitogen phytohaemagglutinin (PHA) and significant increases in mitochondrial oxygen consumption and basal glycolytic activity in PBMC of diabetic pigs. Using LC-MS/MS, we analysed the porcine CD4+ T cell proteome with a total of 2,704 quantified proteins and identified important differences in protein abundances in young diabetic pigs indicating distinct proteomic changes in T cells at initial stage diabetes mellitus.