Exosomes as new players in metabolic organ cross-talk

Blood glucose homeostasis requires a constant communication between insulin-secreting and insulin-sensitive cells. A wide variety of circulating factors, including hormones, cytokines and chemokines work together to orchestrate the systemic response of metabolic organs to changes in the nutritional state. Failure in the coordination between these organs can lead to a rise in blood glucose levels and to the appearance of metabolic disorders such as diabetes mellitus. Exosomes are small extracellular vesicles (EVs) that are produced via the endosomal pathway and are released from the cells upon fusion of multivesicular bodies with the plasma membrane. There is emerging evidence indicating that these EVs play a central role in cell-to-cell communication. The interest in exosomes exploded when they were found to transport bioactive proteins, messenger RNA (mRNAs) and microRNA (miRNAs) that can be transferred in active form to adjacent cells or to distant organs. In this review, researchers from University of Lausanne outline the mechanisms governing the biogenesis, the cargo upload and the release of exosomes by donor cells as well as the uptake by recipient cells. They also summarize the studies that support the novel concept that miRNAs and other exosomal cargo components are new important vehicles for metabolic organ cross-talk.

Schematic representation of the involvement of exosomes in inter-organ cross-talk

Insulin-secreting β-cells and insulin-sensitive tissues release in exosomes containing proteins and microRNA (miRNAs) that can be transferred to other metabolic organs, or to immune or endothelial cells. Exosomes are acting in both autocrine and paracrine manners to favour the maintenance of glucose homeostasis or to aggravate insulin resistance.