Insulin exhibits short-term anti-inflammatory but long-term proinflammatory effects in vitro

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:298

Article

Iwasaki, Yasumasa¹  Nishiyama, Mitsuru¹  Taguchi, Takafumi¹  Asai, Masato²  Yoshida, Masanori²  Kambayashi, Machiko¹  Terada, Yoshio¹  Hashimoto, Kozo¹ 

[1] Kochi Univ, Kochi Med Sch, Dept Endocrinol Metab & Nephrol, Nankoku, Kochi 7838505, Japan

[2] Nagoya Univ, Grad Sch Med, Dept Med, Nagoya, Aichi 4668550, Japan

关键词: Nuclear factor-kappaB;    Insulin;    Phosphatidylinositol 3-kinase;    Mitogen-activated protein kinase;    Atherothrombosis;   

DOI  :  10.1016/j.mce.2008.09.030

来源: Elsevier

【 摘 要 】

Although insulin is indispensable for maintaining glucose homeostaisis, it is still controversial whether or not a high concentration of insulin is deleterious. We examined the effect of insulin on the transcriptional activity of NF-kappa B, which mediates the expression of a variety of inflammation/coagulation-related genes using hepatocyte cell lines in vitro. We found that insulin (1nM) alone caused minimal increase in NF-kappa B-mediated transcription. On the other hand, when cells were simultaneously treated with proinflammatory cytokines such as TNF alpha, the following dual effect of insulin was observed: short-term (6 h) suppressive, and long-term (36 In or later) stimulatory effects. The former effect was transient and appears to be mediated by the phosphatidylinositol 3 kinase (Pl(3)K) signaling pathway. The latter effect, in contrast, was more pronounced, enhancing the TW alpha-stimulated NF-kappa B-dependent transcription by more than sevenfold. This positive effect was NF-kappa B-specific, and was eliminated by mitogen-activated protein kinase (MAPK) inhibitors. Altogether, our data suggest that insulin has short-term anti-inflammatory but long-term proinflammatory effects. From a clinical standpoint, this implies that low basal and periodically high plasma insulin is beneficial, whereas a sustained rise in plasma insulin, as often seen in patients with obesity, may induce atherothrombotic disorders, because of the NF-kappa B-mediated overexpression of proinflammatory/procoagulant/antifibrinolytic proteins in the liver. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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