PT  - JOURNAL ARTICLE
AU  - Freeman, David W.
AU  - Noren Hooten, Nicole
AU  - Eitan, Erez
AU  - Green, Jamal
AU  - Mode, Nicolle A.
AU  - Bodogai, Monica
AU  - Zhang, Yongqing
AU  - Lehrmann, Elin
AU  - Zonderman, Alan B.
AU  - Biragyn, Arya
AU  - Egan, Josephine
AU  - Becker, Kevin G.
AU  - Mattson, Mark P.
AU  - Ejiogu, Ngozi
AU  - Evans, Michele K.
TI  - Altered Extracellular Vesicle Concentration, Cargo, and Function in Diabetes
AID  - 10.2337/db17-1308
DP  - 2018 Nov 01
TA  - Diabetes
PG  - 2377--2388
VI  - 67
IP  - 11
4099  - http://diabetes.diabetesjournals.org/content/67/11/2377.short
4100  - http://diabetes.diabetesjournals.org/content/67/11/2377.full
SO  - Diabetes2018 Nov 01; 67
AB  - Type 2 diabetes is a chronic age-associated degenerative metabolic disease that reflects relative insulin deficiency and resistance. Extracellular vesicles (EVs) (exosomes, microvesicles, and apoptotic bodies) are small (30–400 nm) lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids as part of intercellular communication systems. Recent studies in mouse models and in cell culture suggest that EVs may modulate insulin signaling. Here, we designed cross-sectional and longitudinal cohorts of euglycemic participants and participants with prediabetes or diabetes. Individuals with diabetes had significantly higher levels of EVs in their circulation than euglycemic control participants. Using a cell-specific EV assay, we identified that levels of erythrocyte-derived EVs are higher with diabetes. We found that insulin resistance increases EV secretion. Furthermore, the levels of insulin signaling proteins were altered in EVs from individuals with high levels of insulin resistance and β-cell dysfunction. Moreover, EVs from individuals with diabetes were preferentially internalized by circulating leukocytes. Cytokine levels in the media and in EVs were higher from monocytes incubated with diabetic EVs. Microarray of these leukocytes revealed altered gene expression pathways related to cell survival, oxidative stress, and immune function. Collectively, these results suggest that insulin resistance increases the secretion of EVs, which are preferentially internalized by leukocytes, and alters leukocyte function.