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Human Movement
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2012
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vol. 13
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issue 4
372-379
EN
Purpose. Interleukin-6 (IL-6) belongs to the IL-6-type cytokine family, which, besides IL-6, comprises of IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT) and cardiotrophin-like cytokine (CLC). The metabolic effects of IL-6 differ markedly depending on the nature of the target cell with positive action on nerve cells’ differentiation and hematopoesis, but negative in the etiology of autoimmune disease such as rheumatoid arthritis. In a target cell, IL-6 can simultaneously generate functionally distinct or sometimes contradictory signals depending on the in vivo environment, and the final physiological effect is a consequence of the orchestration of the diverse signals. Thus, its physiological effects are characterized by pleiotropy and redundancy. At present, it has been well documented that in obese individuals, IL-6, as an adipokine secreted into circulation by adipose tissue in proportion to body fat content and an elevated level of the cytokine in the plasma, adversely affects insulin signaling and glucose disposal in skeletal muscles and liver. Moreover, several lines of evidence indicated that IL-6 is a myokine synthesized in skeletal muscle and secreted into the bloodstream in response to exercise. In this way muscular work has a potential to stimulate adipose tissue lipolysis and provides an energy to working muscle. Furthermore, muscle-originated IL-6 acts locally, positively affecting intramuscular fat utilization. It has also been postulated that IL-6 is inevitable for satellite cell stimulation and muscle hypertrophy and repair.
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2015
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vol. 62
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issue 1
15-21
EN
Several relations between cytokines and pathogenesis of diabetes are reviewed. In type 1 and type 2 diabetes an increased synthesis is observed and as well as the release of pro-inflammatory cytokines, which cause the damage of pancreatic islet cells and, in type 2 diabetes, the development of the insulin resistance. That process results in the disturbed balance between pro-inflammatory and protective cytokines. Pro-inflammatory cytokines such as interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as recently discovered pancreatic derived factor PANDER are involved in the apoptosis of pancreatic β-cells. Inside β-cells, cytokines activate different metabolic pathways leading to the cell death. IL-1β activates the mitogen-activated protein kinases (MAPK), affects the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activates the inducible nitric oxide synthase (iNOS). TNF-α and IFN-γ in a synergic way activate calcium channels, what leads to the mitochondrial dysfunction and activation of caspases. Neutralization of pro-inflammatory cytokines, especially interleukin 1β with the IL-1 receptor antagonist (IL-1Ra) and/or IL-1β antibodies might cause the extinction of the inflammatory process of pancreatic islets, and consequently normalize concentration of glucose in blood and decrease the insulin resistance. In type 1 diabetes interleukin-6 participates in regulation of balance between Th17 and regulatory T cells. In type 2 diabetes and obesity, the long-duration increase of IL-6 concentration in blood above 5 pg/ml leads to the chronic and permanent increase in expression of SOCS3, contributing to the increase in the insulin resistance in cells of the skeletal muscles, liver and adipose tissue.
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