Skeletal Muscle and Exercise. How does it Help Preventing Insulin Resistance?

Throughout evolution, exercise in the form of food gathering, shelter seeking, and predator avoidance has been essential for human survival and necessitated the development of an adaptive mechanism to support muscle function and overall health.

In recent years, technological advances have markedly diminished the need for physical activity, which contributes to the development of different human diseases, including insulin resistance and type 2 diabetes that is currently at a pandemic level. 

The benefits of doing physical activity are well known and irrefutable. However, the precise mechanisms by which physical activity promotes metabolic health are not completely understood.  

New Study Results 

Exercise results in skeletal muscle exposure to acute stresses that stimulate compensatory and adaptive physiological responses, which increase the tolerance and protect against subsequent stressors and are considered important for the health-promoting effects of exercise. Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise.

A new study published in the journal Science Advances demonstrated that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance.

They also found that the generation of ROS by skeletal muscle NOX4, the expression of which is increased by exercise and conversely is reduced with age or obesity, induces adaptive responses that prevent oxidative damage, maintain muscle function and exercise capacity, and attenuate the age and obesity-associated development of insulin resistance. 

This dysregulation of redox homeostasis is thought to contribute to the development of many human diseases, particularly insulin resistance and type 2 diabetes. 

The results of the study indicate that skeletal muscle NOX4 is instrumental in orchestrating hormetic responses that attenuate the age-associated development of insulin resistance, hyperinsulinemia, and hyperglycemia, hallmarks of type 2 diabetes. They also underscore the importance of redox balance in metabolic health and provide important insight into the mechanisms contributing to the diabetes pandemic in the aging and increasingly sedentary populations. 


Chrysovalantou E. Xirouchaki, et al. Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance. Sci Adv. 2021. DOI: 10.1126/sciadv.abl4988

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