Investigating the role of altered immune cell metabolism and inflammation in type 2 diabetes
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2020
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University of Hawaii at Manoa
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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.
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38 pages
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