Activation of opioid [mu]-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells

• Published in: Diabetologia 2005-07, Vol.48 (7), p.1386
• Main Authors: T.-F. Tzeng, I.-M. Liu, J.-T. Cheng
• Format: Article
• Language: English
• Subjects: Cytokines; Glucose; Insulin resistance; Kinases; Musculoskeletal system; Narcotics; Phosphorylation; Proteins
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-1791-6

This study investigated the role of opioid mu-receptor activation in the improvement of insulin resistance. Myoblast C2C12 cells were cultured with IL-6 to induce insulin resistance. Radioactive 2-deoxyglucose (2-DG) uptake was used to evaluate the effect of loperamide on insulin-stimulated glucose utilisation. Protein expression and phosphorylation in insulin-signalling pathways were detected by immunoblotting. The insulin-stimulated 2-DG uptake was reduced by IL-6. Loperamide reversed this uptake, and the uptake was inhibited by blockade of opioid mu-receptors. Insulin resistance induced by IL-6 was associated with impaired expression of the insulin receptor (IR), IR tyrosine autophosphorylation, IRS-1 protein content and IRS-1 tyrosine phosphorylation. Also, an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase, Akt serine phosphorylation and the protein of glucose transporter subtype 4 were observed in insulin resistance. Loperamide reversed IL-6-induced decrement of these insulin signals. Opioid mu-receptor activation may improve IL-6-induced insulin resistance through modulation of insulin signals to reverse the responsiveness of insulin. This provides a new target in the treatment of insulin resistance.