“The exosomes were just as effective in reversing insulin resistance as the drug itself but without the same side effects,” said Olefsky. “This indicates that exosomes can ultimately link obesity-related inflammation and insulin resistance to diabetes. It also tells us that we may be able to leverage this system to boost insulin sensitivity.”

The researchers were also able to identify the specific microRNA within the exosomes that was responsible for the beneficial metabolic effects of rosiglitazone. This molecule, called miR-690, could eventually be leveraged into new therapies for type 2 diabetes.

“It’s likely not practical to develop exosomes themselves as a treatment because it would be difficult to produce and administer them, but learning what drives the beneficial effects of exosomes at the molecular level makes it possible to develop drugs that can mimic these effects,” said Olefsky. “There’s also plenty of precedent for using microRNAs themselves as drugs, so that’s the possibility we’re most excited about exploring for miR-690 going forward.” 

Additional authors on the study include: Theresa V. Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha e Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M. Libster, Rizaldy C. Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano and Allen Wang, all at UC San Diego.

This study was funded, in part, by the National Institutes of Health (grants P30DK063491, R01DK101395, DK124298, R00DK115998, R21HD107516, R01DK125560, DK099205, AA028550, DK101737, AA011999, DK120515, AA029019, DK091183), the Swiss National Science Foundation (grant P2BSP3_200177), the Larry L. Hillblom Foundation (grants 2023-D-012-FEL and 2023-D-011-FEL), UCLA LIFT-UP, and Janssen Pharmaceuticals.

Disclosures: Wei Ying and Jerrold Olefsky are co-inventors on a provisional patent covering the use of miR-690 as an insulin sensitizer.