This study examined whether stress inside the mitochondria contributes to insulin resistance in skeletal muscle. Researchers gave healthy participants a lipid infusion to mimic the high levels of circulating fat that are known to impair insulin sensitivity. When participants were also given a compound (MitoQ) that reduces oxidative stress in mitochondria, their muscles were better able to take up glucose in response to insulin.

The improvement did not come from changing the usual insulin-signaling pathways. Instead, reducing mitochondrial stress helped glucose transporters (GLUT4) move to the surface of muscle cells, allowing glucose to enter the cells more easily. In simple terms, the study suggests that when mitochondria become overloaded and produce excess oxidative stress, muscles become more insulin resistant—and protecting mitochondrial function may help maintain normal glucose metabolism.

https://www.science.org/doi/10.1126/sciadv.adq4461