Investigating the role of altered immune cell metabolism and inflammation in type 2 diabetes

Abstract

Type 2 diabetes (T2D) is a worldwide epidemic, with a disproportionate affect on the Native Hawaiian population and economy in Hawaiʻi. Inflammation associated with obesity is a major risk factor in T2D and often preceeds T2D, but the role of inflammation and its link to altered immune cell metabolism and inflammation in T2D is unknown. Thus, there is a need to characterize and understand the inflammatory mechanisms contributing to metabolic abnormalities in T2D. Herein, we characterized and compared innate immune cell metabolism of lymphocytes (T cells, B cells, NK cells) and monocytes in PBMCs and phenotyped inflammatory immune CD4+ and CD8 + T cell subset populations (senescent, naïve, central, intermediate, and effector) in individuals with T2D and controls. First, to characterize and compare immune cell metabolism in individuals with T2D, we compared the metabolic profiles of T2D and healthy control peripheral blood mononuclear cells (PBMCs) by measuring glycolysis and mitochondrial respiration rates on the Agilent Seahorse XFe96 Analyzer. Individuals with T2D showed abnormal altered metabolic function of immune cells by decreasing glycolysis and increasing oxidative phosphorylation in PBMCs. Second, to phenotype and quanitfy the immune cell subset populations in individuals with T2D, we used a BD LSR Fortessa flow cytometer capable of detecting fluorochrome-conjugated antibodies specific for markers of particular immune cell subsets. Inflammatory CD8+ central memory T cells were increased and CD8+ naïve T cells were decreased in T2D compared to controls. In summary, this project helped fill a gap in knowledge on the role of altered cellular metabolism and the immune cell types that may contribute to disease. Moreover, this novel information may be relevant for improving the treatment and management of T2D.