**Author details**

is a predominance of the β-oxidation of fatty acids synthesis, and the production of energy outweighs the expense [72, 73]. Considering intervention strategies for T2DM, exercise improves muscular oxidative capacity and, consequently, insulin sensitivity, up regulating the expression of PGC-1α in healthy subjects. In many rodent models, the increase of the OXPHOS is coordinated by PGC-1α, which increases the transcriptional activity of PPARγ, reducing the

The predominant oxidative metabolism in type I fibers, which are modified by the action of aerobic training at moderate or high intensity, may be a key point to glucose metabolism regulation. There is an increase in the number of mitochondria and GLUT4 vesicles, thus promoting the acceleration of oxidative metabolism with increased ROS production accom‐ panied by increased antioxidant defense capacity. Increase in antioxidant enzyme activity observed in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and also in glutathione (GSH) content, represent oxidative stress preventive adaptations induced by exercise training. The redox protection has direct impact in the maintenance of insulin sensitivity in the muscle [74, 75]. These changes may be triggered or

Regular exercise promotes the acute increase of blood flow and shear stress and, in turn, improves the NO bioavailability, hence increasing the endothelium-dependent vasodilatation. This NO effect occurs in parallel to the decrease in pro-inflammatory biomarkers after exercise training. This improvement in NO and decrease in pro-inflammatory markers could represent one of the most important mechanisms of cardioprotection induced by regular exercise that prevent comorbidities associated to T2DM. However, the exercise intensity seems to be a crucial variable to future studies. iHSP70 expression depends on exercise intensity (level of physical challenge, measured by workload or time), while many other adaptations could not be influenced by exercise training intensity. We believe that exercise can induce both intracel‐ lular and extracellular HSP70, but promotes equilibrium in HSP70 signaling to the whole body

Exercise is a known modulator of all parameters listed above: glycemia, eHSP70, iHSP70, IL-6, TNF-α, and ROS. Intracellular and extracellular HSP70 have different roles in the regulation of "immune-metabolic" homeostasis as well as cytokines. Equilibrium is also obtained by exercise in redox state by improving antioxidant defenses in the muscle and between pro/antiinflammatory cytokines production. Reduction or prevention of obesity by active muscles can be considered key to the process. By metabolic and anti-inflammatory effects, exercise represents a good and safe strategy against insulin resistance induced by age and lifestyle

effects that promote insulin resistance.

98 Muscle Cell and Tissue

stimulated by increased HSP70 expression [76].

in T2DM [77, 78].

**5. Conclusion**

factors (Figure 4).

Thiago Gomes Heck1,2\*, Mirna Stela Ludwig1,2, Analu Bender dos Santos1 and Pauline Brendler Goettems-Fiorin1,3

\*Address all correspondence to: gomesheck@yahoo.com

1 Research Group in Physiology. Department of Life Sciences, Regional University of Northwestern State's Rio Grande do Sul (UNIJUI), Ijuí, RS, Brazil

2 Postgraduate Program in Integral Attention to Health (PPGAIS-UNIJUI/UNICRUZ), Ijuí, RS, Brazil

3 Postgraduate Program in Health Sciences (PPGCS-UFCSPA), Porto Alegre, RS, Brazil

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