Department of Endocrinology, Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, China.
Hepatobiliary Pancreat Dis Int. 2010 Feb;9(1):49-53.
It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance.
Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was performed with [6-3H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits.
Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05).
Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappaB provide potential pathogenic links to oxidative stress.
有报道称，大剂量水杨酸盐可改善体外游离脂肪酸（FFAs）诱导的胰岛素抵抗和β细胞功能障碍，但机制尚不清楚。在胰岛素抵抗大鼠中，我们发现补充水杨酸钠与血浆丙二醛（MDA）的减少有关，MDA 是氧化应激的标志物。很少有研究调查水杨酸盐对胰岛素抵抗动物模型中氧化应激水平的影响。本研究旨在评估水杨酸钠对胰岛素敏感性的影响，并探讨其改善肝和外周胰岛素抵抗的潜在机制。
正常 Wistar 大鼠分别输注脂肪乳剂+肝素（IH）、生理盐水（SAL）或脂肪乳剂+肝素+水杨酸钠（IHS）7 小时。在输注的最后 2 小时内，使用 [6-3H] 葡萄糖示踪剂进行高胰岛素-正常血糖钳夹。用葡萄糖氧化酶法测定血浆葡萄糖。用放射免疫法测定血浆胰岛素和 C 肽。用比色法试剂盒测定肝和骨骼肌中的 MDA 水平和谷胱甘肽过氧化物酶（GSH-PX）活性。
与 SAL 输注相比，IH 输注增加了肝葡萄糖生成（HGP），并降低了葡萄糖利用（GU）（P<0.05）。游离脂肪酸的升高增加了肝和肌肉中的 MDA 水平，并降低了 GSH-PX 活性（P<0.01）。水杨酸钠处理降低了 HGP，升高了 GU（P<0.05），降低了 MDA 含量 60%（P<0.01），并增加了 GSH-PX 活性 35%（P<0.05）。
短期升高脂肪酸会通过增强肝和肌肉中的氧化应激水平来诱导胰岛素抵抗。抗炎药物水杨酸钠的给药可降低氧化应激程度，从而改善肝和外周胰岛素抵抗。IKK-β和 NF-κB 为氧化应激提供了潜在的致病联系。
