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The Effects of Oxidative Stress on Insulin Resistance

With the holiday’s right around the corner, many of us are probably dreading the added holiday pounds. But what, exactly, causes the insulin resistance that ultimately leads to weight gain?

Studies in rodents led to the discovery that overeating leads to insulin resistance before weight gain. Possible mechanisms proposed and studied by researchers were elevated fatty acid levels, inflammation, endoplasmic reticulum (ER) stress, and oxidative stress. In a recent study published in Science Translational Medicine, Temple University researchers studied six healthy men voluntarily confined to a hospital bed for a week and given a 6,000 calorie/day diet.

What researchers found in the six healthy men was that, as expected, insulin resistance developed rapidly by day two. But there was no increase in fatty acids, no inflammation, and no signs of ER stress. However, they found that oxidative stress increased at approximately the same rate as insulin resistance.

The researchers speculated that one possible mechanism by which oxidative stress caused insulin resistance is oxidation of the intracellular glucose transporter GLUT4, which is dependent on insulin signaling to move vesicles to the cell membrane. When the study subject’s fat tissue was examined, researchers saw that the structure of GLUT4 had been modified, rendering it dysfunctional. One of the modifications was cabonylation, which has been known to affect protein function.

Do you think this study of rapid and extreme overeating was realistic enough to extrapolate the results to how insulin resistance normally develops? Also, the participants in this study were completely inactive. What role does physical activity play in the development of insulin resistance in high caloric diets? Some think it may exacerbate it, since exercise can lead to the production of more reactive oxygen species (ROS). What do you think?

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Enzo Life Sciences sells a wide range of products to analyze the origins and consequences of oxidative stress.

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