N. Houstis et al., "Reactive oxygen species have a causal role in multiple forms of insulin resistance," Nature, 440:944—8, 2006. (Cited in 109 papers)
Evan Rosen, from Beth Israel Deaconess Medical Center in Boston, and other colleagues tested whether a common mechanism underlies the various stimuli that cause cells to become insulin resistant. Using transcriptional profiling in mouse cell culture, they found about 80 gene changes common between two stimuli (mouse tumor necrosis factor [TNF] and the glucocorticoid dexamethasone), most of them relating to reactive oxygen species (ROS) activities.
The authors also observed in cell culture and in mice that increased ROS levels prompted insulin resistance, and lower ROS levels reduced resistance by roughly 50%. "This paper was the first convincing, comprehensive evidence that reactive oxygen species cause insulin resistance," says James Meigs at Massachusetts...
Meigs and his colleagues took data from the Framingham Offspring Study and found that, in humans, markers of oxidative stress are associated with markers of insulin resistance ( Diabetes Care, 30:2529—30, 2007).
The next step:
Rosen says he would like to determine the origin of ROS in the cell, and exactly how they cause insulin resistance. "There are lots of candidate pathways," such as FoxO, JNK, and PI3K, Rosen says. "I don't think it's going to be one thing."
|Antioxidants decrease insulin resistance|
|Cause of Insulin Resistance||Antioxidant||% Recovery in Insulin Sensitivity|
|Tumor necrosis factor- ||MnTBAP||60|
|Tumor necrosis factor- ||N-acetylcysteine||25|