Insulin is a pleiotropic hormone, which under normal conditions determines intensity of the metabolism of carbohydrates, proteins and lipids. Insulin regulates many processes. It stimulates glucose transport, protein synthesis and glycogen synthesis as well as it inhibits lipolysis and regulates cell survival (1). The insulin action on the target cells is dependent on a specific membrane receptor IR (insulin receptor). The highest number of IRs is observed on the surface of adipocytes, hepatocytes and miocytes. Activated receptor initiates a cascade of protein kinase phosphorylation. Insulin activates two main signaling pathways. The first one is the phosphatidylinositol 3-kinase (PI3-K) pathway, which stimulates cell growth, survival, differentiation and homeostasis of the metabolism. The second one is the Ras-mitogen activating protein kinase (Ras-MAPK) pathway, which regulates gene expression and determines the cell proliferation (2).

Impairment of the insulin signaling leads to disturbed glucose homeostasis and results in decreased tissues insulin sensitivity. The state described above is known as an insulin resistance. Insulin resistance affects many tissues and organs, especially the skeletal muscles, liver, adipocytes and brain. Up to date, three types of disturbances have been described, all of which result in the development of insulin resistance:

1. The pre-receptor insulin resistance being related to the genetically incorrect structure of the insulin molecule.

2. Insulin resistance may result also from receptor abnormalities. Mutations in the gene encoding the insulin receptor were found in patients with inherited insulin resistance (3). These mutations result in a lack of ability of the insulin receptor to transmit insulin signaling to the target cell.

3. The post-receptor level abnormalities, including abnormal course of metabolic pathways, disturbed structure and function of regulatory proteins, and impaired glucose transport, can also induce insulin resistance. In addition to the genetic factors also environmental factors such as obesity, physical inactivity and sedentary lifestyle contribute to the decreased insulin sensitivity. In this review we would like to summarize the current knowledge of endocrine crosstalk between skeletal muscles and adipose tissue, and their effect on insulin action.

According to data presented by the World Health Organization (WHO) obesity has reached epidemic proportions. In the European countries, the problem of overweight and obesity concerns 30-80% of adults. It was also found that almost 20% of children and adolescents is overweight, and one in three is obese (4). Obesity is a major factor of morbidity and mortality, associated with increased risk of development of several diseases such as hypertension, coronary heart disease, atherosclerosis, dyslipidemia, type 2 diabetes and certain types of cancer. Moreover, the last epidemiological studies indicated that obesity also predisposes to the development of neuroinflammation and neurodegenerative diseases.

It is now believed that adipose tissue (AT) is not only a storage depot of the energy, but also it is considered to be the largest endocrine organ that produces and secretes several factors called adipokines. Adipokines through autocrine, paracrine and endocrine action are involved in the regulation of many processes, such as food intake, insulin secretion, insulin sensitivity, energy expenditure, inflammation and the function of the cardiovascular system (5). AT is composed of preadipocytes, adipocytes, endothelial cells, mesenchymal stem cells and immune cells (monocytes and macrophages), which have a secretory activity (6). The large group of bioactive adipocyte-derived protein molecules includes: leptin, adiponectin, resistin, visfatin, chemerin, tumor necrosis factor (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) (7) and others. Excessive accumulation of adipose tissue mass leads to dysregulation of the expression of adipokines and, in consequence, to development of many pathological conditions. Moreover, obesity is associated with increased macrophage infiltration, endothelial cell activation and fibrosis (8). In the recent years, special attention has been paid to the relationship between adiposity, inflammation and the development of insulin resistance. Actually, several potential mechanisms have been suggested to be as involved in the development of obesity-associated insulin resistance.

1. The metabolic hypothesis assumes that enhanced plasma free fatty acid (FFA) concentration results in an increase in intracellular longchain Acyl-CoA, diacylglycerol (DAG) and ceramides concentrations. Consequently these factors cause an activation of protein kinases, such as protein kinase C (PKC) isoforms (9), the inhibitor of nuclear factor-κB kinase-β (IKKβ), and Jun kinase (JNK) (10). Then, activated kinases can impair insulin signaling by increasing the inhibitory serine phosphorylation of insulin receptor substrates 1 (IRS-1), which in turns lead to decreased IRS-1 tyrosine phosphorylation (11).