Expression of chemokine receptors in insulin-resistant human skeletal muscle cells

Horm Metab Res. 2007 Apr;39(4):244-9. doi: 10.1055/s-2007-972577.

Abstract

Adipokines including chemokines are able to induce insulin resistance in human skeletal muscle cells, which may also be relevant for the observed link between obesity and diabetes. This study is aimed to analyze the expression of chemokine CC motif receptors (CCRs) in the insulin-resistant state in human skeletal muscle cells. Differentiated skeletal muscle cells were incubated for 24-72 hours with high concentrations of glucose and insulin (GI) or TNFalpha. In addition, myocytes were co-stimulated with monocyte chemotactic protein (MCP)-1 or adipocyte-conditioned medium (CM) and TNFalpha for 24 and 48 hours. Treatment with GI rapidly induced insulin resistance whereas TNFalpha impaired insulin signaling in a more chronic fashion (48-72 h). CM and MCP-1 also induced insulin resistance that was, however, not increased by co-stimulation with TNFalpha. Expression of CCR2 was decreased during differentiation but up-regulated in insulin-resistant myocytes after treatment with GI (24-72 h) and TNFalpha (72 h). Expression of CCR4 and CCR10 was down-regulated after treatment with TNFalpha, MCP-1, and CM. Our data show that the expression of CCR2, CCR4, and CCR10 is differentially regulated by different insulin resistance-inducing treatments in myotubes. However, we could not find a clear correlation between the level of insulin resistance and CCR expression in myotubes. In conclusion, we propose that upregulation of CCR2 in skeletal muscle does not represent a major step leading to muscle insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Differentiation / physiology
  • Child
  • Child, Preschool
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Glucose / pharmacology
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Receptors, CCR10
  • Receptors, CCR2
  • Receptors, CCR4
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • Tubulin / biosynthesis
  • Tubulin / genetics
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects

Substances

  • CCR10 protein, human
  • CCR2 protein, human
  • CCR4 protein, human
  • Hypoglycemic Agents
  • Insulin
  • Receptors, CCR10
  • Receptors, CCR2
  • Receptors, CCR4
  • Receptors, Chemokine
  • Tubulin
  • Tumor Necrosis Factor-alpha
  • Glycogen Synthase Kinase 3
  • Glucose