Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells

Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic beta cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic beta cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E beta cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused beta cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-beta H3 beta cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of beta cell genes, adipokines, and cytokines in recipient beta cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence beta cell fate and function.

Automated summary

Healthy adipocyte-derived EVs are beneficial for beta cell survival and function, while EVs from inflamed adipocytes cause beta cell death and dysfunction. Lean adipocyte-derived EVs have similar beneficial effects, whereas EVs from obese adipose tissue are harmful for beta cells. Differential expression of miRNAs and alterations in signaling pathways and gene expression in recipient beta cells were observed, suggesting that adipocyte-derived EVs may influence beta cell fate and function depending on the physiological and pathological state of adipose tissue.