High Insulin and Leptin Increase Resistin and Inflammatory Cytokine Production from Human Mononuclear Cells

High Insulin and Leptin Increase Resistin and Inflammatory Cytokine Production from Human Mononuclear Cells

Resistin and the proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-1 beta, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF-alpha, IL-6, and IL-1 beta production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subseuent addition of high glucose significantly upregulated resistin and TNF-alpha mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1 beta production. By comparison, exposure to dexamethasone reduced TNF-alpha, IL-6, and IL-1 beta production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-alpha, IL-6, and IL-1 beta from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

Tsiotra, Panayoula C. Boutati, Eleni Dimitriadis, George and Raptis, Sotirios A.

2013