Author:
Lappas Martha,Yee Kirin,Permezel Michael,Rice Gregory E.
Abstract
There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-κB (NF-κB) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-κB regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-κB inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 μm). After an 18-h incubation, the tissues were collected, and NF-κB p65 DNA-binding activity and IκB kinase (IKK-β) and insulin receptor-β protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-α, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-α; NF-κB p65 DNA-binding activity; and IKK-β protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-β. The data presented in this study demonstrate that the IKK-β/NF-κB transcription pathway is a key regulator of IL-6, IL-8, and TNF-α release from adipose tissue and skeletal muscle. Control of the IKK-β/NF-κB pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.
Cited by
87 articles.
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