Chemerin induces insulin resistance in rat cardiomyocytes in part through the ERK1/2 signaling pathway

Pharmacology. 2014;94(5-6):259-64. doi: 10.1159/000369171. Epub 2014 Nov 28.

Abstract

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-α), 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.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Chemokines / metabolism*
  • Flavonoids / pharmacology
  • Glucose / pharmacology
  • Insulin / pharmacology
  • Insulin Resistance
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Rats, Sprague-Dawley
  • Receptors, Chemokine / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemokines
  • Cmklr1 protein, rat
  • Flavonoids
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Rarres2 protein, rat
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases
  • Glucose
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one