**Lifestyle and Aging Effects in the Development of Insulin Resistance — Activating the Muscle as Strategy Against Insulin Resistance by Modulating Cytokines and HSP70**

Thiago Gomes Heck, Mirna Stela Ludwig, Analu Bender dos Santos and Pauline Brendler Goettems-Fiorin

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/60895

#### **Abstract**

This chapter discusses about subclinical processes related to insulin resistance development that worsen the muscle metabolic functions, generated by factors such as lifestyle (bad quality food intake and sedentary behavior) and aging. Also discussed are the effects of regular physical exercise as a strategy to prevent the metabolic impairment in organisms, approaching since muscle subclinical molecular processes to the whole body's integrative physiology. Insulin resistance development includes modification in the pattern of inflammatory cytokines, heat shock proteins, tissuespecific defects in insulin action and signaling, oxidative stress and ectopic lipid deposition. The exercise is a known modulator of all parameters listed above and has important role in the regulation of "immune-metabolic" homeostasis from the muscle to the whole body. This chapter aims to present a new molecular approach related to the control of metabolism and encourage scientists and students to propose new strategies against insulin resistance and diabetes type 2 developments.

**Keywords:** Insulin resistance, exercise, heat shock proteins, cytokines, oxidative stress

### **1. Introduction**

Metabolism can be defined as the sum of all reactions that occur in the whole body, from cells to complex system, with a multi-organ talk about energy transfer, signaling, and then regula‐

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tory pathways of metabolic status. One of the most important parameters of human metabolic homeostasis is glycemia that results from the availability and the utilization of nutrient sources. In this way, the cellular uptake and glycogenesis in skeletal muscle fibers have important implications in the regulation of blood glucose. This metabolic process was regulated by insulin that acts on muscle promoting the translocation of glucose transporter-4 (GLUT4), which is the most abundant insulin-dependent transporter in the cell membranes of the skeletal muscle, heart muscle, and adipose tissue, which leads to the uptake of glucose into the cell.

In this scenario, the muscle can be considered an important organ in glucose metabolism regulation, functioning at the same time as locus of start- and end-point of metabolic disorders related to glucose metabolism, and also the key organ of intervention strategies against insulin resistance. This chapter proposes an overview about effects of physical activity and exercise in the muscle as a strategy against insulin resistance. The physiological approach in this chapter is based on two major signaling pathways and biomarkers of muscle function, as well as its interaction with other cells and tissues—the cytokines and heat shock proteins (HSPs).

Skeletal muscle contains anatomic and physiological characteristics that represent different possibilities and functions in terms of metabolic properties and also in contractility and mitochondrial activity. There are three important factors that influence these characteristics: age, the dietary behavior, and the levels of physical activity. Together, these factors determine the muscle health status and capacity of physical performance, then, consequently, the whole body homeostasis. Aging, high caloric diet consumption, and sedentary behavior leads the progression of the muscle dysfunction that culminates in the loss of metabolic homeostasis, promoting dyslipidemia and glycemic alterations.

However, these outcomes are presented in the established metabolic disease, while many subclinical processes precede the onset of disease. Subclinical modifications also accom panied the undesired progression of metabolic disease, increased the incidence of comorbidities and increased hospital admissions. These silent subclinical effects, such as inflammation, oxidative stress, and molecular alterations, decreased gradually the individual health status and decreased the quality of life (Figure 1).

**Figure 1.** Muscle as the target of subclinical modification related to metabolic disease development.

Thus, in this chapter we first discussed factors that worsen the muscle's subclinical metabolic functions, such as lifestyle (bad quality food intake and sedentary behavior) and aging; second we discussed about the effects of exercise as a strategy to prevent metabolic impairment, in the maintenance of muscle health, and to improve body homeostatic control, from the muscle's subclinical molecular processes to the whole body.
