Chemerin Induces Insulin Resistance in Rat Cardiomyocytes in Part through the ERK1/2 Signaling Pathway

Aims: Chemerin is a novel adipokine that is closely associated with cardiovascular diseases and glucose homeostasis. This study aimed to investigate the effects of chemerin on insulin resistance in rat cardiomyocytes. Methods: Rat cardiomyocytes were treated with high concentrations of glucose and tumor necrosis factor-alpha (TNF-alpha), and chemerin and chemokine-like receptor 1 (CMKLR1) were measured by Western blot analysis. Then, the cardiomyocytes were treated with chemerin and insulin. Glucose uptake was evaluated using a fluorescence microplate reader. Western blot analysis was used to evaluate the phosphorylation of Akt, insulin receptor substrate-1, p38 mitogen-activated protein kinase (MAPK), as well as extracellular signal-regulated kinase (ERK) 1/2. Results: Chemerin and CMKLR1 were found to be expressed in rat cardiomyocytes. Pretreatment with chemerin caused decreases in glucose uptake and phosphorylation of Akt in insulin-stimulated cardiomyocytes. Furthermore, chemerin activated the phosphorylation of p38 MAPK and ERK1/2 in insulin-stimulated cardiomyocytes. Inhibition of ERK partially rescued chemerin-induced insulin resistance. Conclusion: Chemerin is a novel adipokine that induces insulin resistance in rat cardiomyocytes in part through the ERK1/2 pathway. (C) 2014 S. Karger AG, Basel