2192-P: Extracellular Vesicles as Novel Mediators of Proinflammatory Cytokine-Induced ß-Cell Dysfunction

The presence of a proinflammatory islet microenviroment and consequent dysregulation of glucose-stimulated insulin secretion (GSIS) is a hallmark feature of both type 1 and type 2 diabetes. Recent evidence has implicated islet cell-derived extracellular vesicles (EVs) as novel mediators of cytokine-derived inflammatory stress in diabetes, however the mechanisms governing this process remain largely unknown. Therefore, we set out to test the hypothesis that cytokine-mediated β-cell dysfunction is mediated in part through β-cell autocrine release of proinflammatory EVs which promote inflammation and inhibit GSIS. Particle size analysis of EVs from conditioned media of cytokine treated (IL-1β, TNF-α, and IFNγ) Min6 β-cells (CytoEV) showed an overall increase in β-cell EV secretion (∼2 fold increase, P Disclosure N. Javeed: None. T.K. Her: None. P.M. Vanderboom: None. I.R. Lanza: None. A. Matveyenko: None.