Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin-Stimulated Glucose Uptake

Abstract

Scope: We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results: EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin-stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin-stimulated 2-deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin-mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2-deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion: EVs released by stressed adipocytes impair insulin action in neighboring adipocytes.