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192 | APRIl 2021 | volume 17 Insulin resistance is a key feature of type 2 diabetes mellitus, but very few therapeutic approaches specifically target this characteristic. New research published in Cell Metabolism suggests that miR-690, which is derived from the exosomes of M2polarized bone marrowderived macrophages (BMDMs), could be used to improve insulin sensitivity. Previous work had demonstrated that exosomes from M2like adipose tissue macrophages in lean mice could be used to ameliorate insulin sensitivity in obese mice. However, this technique had practical limitations and so was challenging to study further. “To overcome these limita tions, we treated mouse BMDMs in vitro with IL-4 and IL-13 to direct them towards an antiinflammatory M2like phenotype and harvested the exosomes they secreted,” explain authors Jerrold Olefsky and Wei Ying. The researchers used the secreted exosomes to treat adipocytes, myocytes and primary mouse hepatocytes in vitro; the exosomes were also administered to mice with highfat dietinduced obesity. Compared with control conditions, the treatment with exosomes improved insulin sensitivity. Exosomes contain a range of factors (including miRNAs), and so, to determine which factor was key in the insulinsensitizing effect, the researchers generated a mouse model that produced exosomes that did not contain miRNAs. When these exosomes were used to treat adipocytes, myocytes and obese mice, no insulinsensitizing effects were seen. The researchers then conducted further experiments with the five most highly expressed miRNAs in BMDM exosomes, which revealed that miR-690 was the factor underlying the insulinsensitizing effect D I a B E T E S