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Diabetologia

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01-07-2005 | Article

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

Authors: T.-F. Tzeng, I.-M. Liu, J.-T. Cheng

Published in: Diabetologia | Issue 7/2005

Abstract

Aims/hypothesis

This study investigated the role of opioid μ-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 μ-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/interpretation

Opioid μ-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.

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Title: Activation of opioid μ-receptors by loperamide to improve interleukin-6-induced inhibition of insulin signals in myoblast C2C12 cells
Authors: T.-F. Tzeng
I.-M. Liu
J.-T. Cheng
Publication date: 01-07-2005
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 7/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-005-1791-6

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

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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