Activation of opioid mu-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells.
OBJECTIVE
This study investigated the role of opioid mu-receptor activation in the improvement of insulin resistance.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tzeng
T-F
TF
Department of Internal Medicine, Pao Chien Hospital, Ping Tung City, Taiwan, Republic of China.
Liu
I-M
IM
Cheng
J-T
JT
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003847:Deoxyglucose / Q000493:pharmacokinetics; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008139:Loperamide / Q000494:pharmacology*; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D015850:Interleukin-6; D010750:Phosphoproteins; D017450:Receptors, Opioid, mu; D009270:Naloxone; D008139:Loperamide; D003847:Deoxyglucose