S-腺苷-L-蛋氨酸可改善 TNFα诱导的 3T3-L1 脂肪细胞胰岛素抵抗。
S-Adenosyl-L-methionine ameliorates TNFalpha-induced insulin resistance in 3T3-L1 adipocytes.
机构信息
Department of Internal Medicine, Eulji University School of Medicine, Seoul 139-872, Korea.
出版信息
Exp Mol Med. 2010 May 31;42(5):345-52. doi: 10.3858/emm.2010.42.5.036.
Abstract
An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The IkappaB kinase-beta (IKK-beta)/ nuclear factor-kappaB (NF-kappaB) pathway is a molecular mediator of insulin resistance. S-Adenosyl-L-methionine (SAM) has both antioxidative and anti-inflammatory properties. We investigated the effects of SAM on the glucose transport and insulin signaling impaired by the tumor necrosis factor alpha (TNFalpha) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNFalpha. The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. In addition, SAM significantly attenuated the TNFalpha-induced degradation of IkappaB-alpha and NF-kappaB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-beta in vitro. These results suggest that SAM can alleviate TNFalpha mediated-insulin resistance by inhibiting the IKK-beta/NF-kappaB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.
摘要
炎症过程与胰岛素抵抗的发病机制之间的关联已被越来越多地提出。IkappaB 激酶-β（IKK-β）/核因子-κB（NF-κB）途径是胰岛素抵抗的分子介质。S-腺苷甲硫氨酸（SAM）具有抗氧化和抗炎作用。我们研究了 SAM 对肿瘤坏死因子α（TNFalpha）在 3T3-L1 脂肪细胞中引起的葡萄糖转运和胰岛素信号受损的影响。SAM 部分逆转了基础状态和胰岛素刺激的葡萄糖转运，而 TNFalpha 则会抑制葡萄糖转运。SAM 还逆转了 TNFalpha 诱导的胰岛素受体底物-1（IRS-1）和 Akt 的酪氨酸磷酸化的抑制。此外，SAM 显著减弱了 TNFalpha 诱导的 IkappaB-α降解和 NF-κB 激活。有趣的是，SAM 在体外直接抑制了 IKK-β的激酶活性。这些结果表明，SAM 通过抑制 IKK-β/NF-κB 途径可以减轻 TNFalpha 介导的胰岛素抵抗，因此在治疗 2 型糖尿病方面可能具有有益作用。
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