Glycated albumin stimulates expression of inflammatory cytokines in muscle cells

The effects of glycated albumin on the expression of inflammatory cytokines in differentiated myotubes were investigated. Glycated albumin stimulates the expression of TNF alpha, IL-1 beta, IL-6 and CCL-2 both at the mRNA and protein levels via the receptor of AGEs. Various cytokines demonstrated different kinetics of stimulation by glycated albumin. At a high glucose concentration, the stimulation effect was more pronounced than at a low one. At physiological concentrations of albumin and fructosamine, the stimulation effect of glycated albumin on inflammatory cytokine expression in myotubes was also observed. The induction of expression of all studied cytokines was sensitive to the inhibitors of JNK, p38 MAPK, MEK1/2, Src family protein kinases and NF-kappa R. At the same time, the induction of TNF alpha and IL 1 beta was diminished by the Ca(2+)calmodulin-dependent protein kinase inhibitor, whereas the induction of IL-6 and CCL-2 was reduced by the inhibitor of phosphoinositide 3-kinase. Possible implications of observed stimulation of cytokine expression by glycated albumin in the development of diabetes mellitus symptoms are discussed.