Inhibitory effect of IL-8 on insulin action in human adipocytes via MAP kinase pathway

Chikaaki Kobashi,Sachie Asamizu,Kazuyuki Tobe,Masaharu Urakaze,Masashi Kobayashi,Isao Usui,Manabu Ishiki,Minoru Iwata,Katusuya Yamazaki

doi:10.1186/1476-9255-6-25

Abstract

BackgroundVarious cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue. They might be involved in complications associated with obesity and diabetes. Recently, interleukin-8 (IL-8) has been shown to be produced and released from human adipose tissue and/or adipocytes, suggesting IL-8 involvement in some obesity-related health complications. Therefore, we found it of interest to investigate whether IL-8 is involved in the insulin action in human adipocytes.MethodsThe IL-8 levels in the medium were measured using ELISA. The IL-8 mRNA expression was analyzed using Northern blot analysis. The phosphorylation of Akt was analyzed using Western blot analysis. Furthermore, we examined the effect of IL-8 on the phosphorylation of Akt induced by insulin.ResultsThe level of IL-8 in the medium and the IL-8 mRNA expression after stimulation with either TNF-α, IL-1β, or CRP was significantly enhanced in human adipocytes. It is particularly interesting that IL-8 per se also enhanced IL-8 mRNA expression. The IL-8 induced-IL-8 mRNA expression was inhibited by PD98059 (a MEK inhibitor) or SB203580 (a p38 MAPK inhibitor). The IL-8 inhibited insulin-induced Akt phosphorylation. The inhibitory effect of IL-8 was eliminated by either PD 98059 or SB203580.ConclusionThese data suggest that IL-8 is a main adipocytokine producing insulin resistance via the inhibition of insulin-induced Akt phosphorylation in adipocytes. The attenuation of IL-8 action might be a target for prevention of diabetes and its complications.

Highlights

Various cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue
We show that the IL-8 production in human adipocytes is enhanced by inflammatory substances such as Tumor necrosis factor-α (TNF-α), IL-1β, and CRP, and we examined the effect of IL-8 on insulin-induced Akt phosphorylation in adipocytes
IFLi-g8umreRN1 A expression induced by IL-8 in human adipocytes IL-8 mRNA expression induced by IL-8 in human adipocytes

Summary

Introduction

Various cytokines and other compounds are produced in human adipose tissue and might have functions in the adipose tissue They might be involved in complications associated with obesity and diabetes. Insulin resistance is defined as the impaired ability of target tissues of fat, liver, and muscle to show various metabolic effects of insulin, including glucose uptake [1]. It is probably caused by defects in the insulin signal transduction pathways [2,3]. Tumor necrosis factor-α (TNF-α) is elevated in obesity and may contribute to many aspects of adipose tissue biology including development of insulin resistance and abnormalities in lipid metabolism. Hauner et al have reported that TNF-α down-regulates the insulin-sensitive glucose transporter GLUT-4, decreasing glucose uptake in adipocytes [10]

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