Proinflammatory Cytokines Alter Beta-Cell Exosome Cargo And Function To Enhance Activation Of The Cxcl10-Cxcr3 Axis In Diabetes

Coordinated activity among islet cells is necessary for glucose homeostasis. Chronic exposure to diabetogenic factors such as pro-inflammatory cytokines, perturbs islet cell crosstalk and β-cell function in diabetes. Secretory nanovesicles - exosomes (EXO) derived from cytokine exposed β-cells modulate physiological and pathological responses to β-cell stress. However, the mechanisms governing this process remain unknown. We tested the hypothesis that β-cell failure in diabetes is mediated in part through β-cell autocrine release of pro-inflammatory EXO to promote inflammation and inhibit β-cell function. Assessment of EXO concentrations from Min6 β-cells exposed to diabetogenic cytokines (IL-1β, TNF-α, and IFNγ, cytoEXO) revealed a 2-fold increase in EXO secretion (p Disclosure N. Javeed: None. T.K. Her: None. M. Brown: None. P.M. Vanderboom: None. A.M. Egan: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc. I.R. Lanza: None. T. Patel: None. A. Matveyenko: None.