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首页> 外文期刊>Cellular Physiology and Biochemistry >Early phase of allergic airway inflammation in diabetic rats: Role of insulin on the signaling pathways and mediators
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Early phase of allergic airway inflammation in diabetic rats: Role of insulin on the signaling pathways and mediators

机译：糖尿病大鼠过敏性气道炎症的早期：胰岛素在信号传导途径和介质中的作用

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Background: Allergic lung inflammation is impaired in diabetic rats and is restored by insulin treatment. In the present study we investigated the effect of insulin on the signaling pathways triggered by allergic inflammation in the lung and the release of selected mediators. Methods: Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and matching controls were sensitized by s.c. injections of ovalbumin (OA) in aluminium hydroxide, 14 days before OA (1 mg/0.4 ml) or saline intratracheal challenge. A group of diabetic rats were treated with neutral protamine Hagedorn insulin (NPH, 4 IU, s.c.), 2 h before the OA challenge. Six hours after the challenge, bronchoalveolar lavage (BAL) was performed for mediator release and lung tissue was homogenized for Western blotting analysis of signaling pathways. Results: Relative to non-diabetic rats, the diabetic rats exhibited a significant reduction in OA-induced phosphorylation of the extracellular signal-regulated kinase (ERK, 59%), p38 (53%), protein kinase B (Akt, 46%), protein kinase C (PKC)- α (63%) and PKC-δ (38%) in lung homogenates following the antigen challenge. Activation of the NF-κB p65 subunit and phosphorylation of IκBα were almost suppressed in diabetic rats. Reduced expression of inducible nitric oxide synthase (iNOS, 32%) and cyclooxygenase-2 (COX-2, 46%) in the lung homogenates was also observed. The BAL concentration of prostaglandin (PG)-E_2, nitric oxide (NO) and interleukin (IL)-6 was reduced in diabetic rats (74%, 44% and 65%, respectively), whereas the cytokine-induced neutrophil chemoattractant (CINC)-2 concentration was not different from the control animals. Treatment of diabetic rats with insulin completely or partially restored all of these parameters. This protocol of insulin treatment only partially reduced the blood glucose levels. Conclusion: The data presented show that insulin regulates MAPK, PI3K, PKC and NF-κB pathways, the expression of the inducible enzymes iNOS and COX-2, and the levels of NO, PGE_2 and IL-6 in the early phase of allergic lung inflammation in diabetic rats. It is suggested that insulin is required for optimal transduction of the intracellular signals that follow allergic stimulation.
机译：背景：糖尿病大鼠的肺部过敏性炎症受损，并通过胰岛素治疗得以恢复。在本研究中，我们研究了胰岛素对肺部过敏性炎症触发的信号通路和所选介质释放的影响。方法：通过s.c.致敏糖尿病雄性Wistar大鼠（四氧嘧啶，42mg / kg，静脉内，10天）和匹配的对照。在OA（1 mg / 0.4 ml）或盐水气管内攻击前14天，在氢氧化铝中注射卵清蛋白（OA）。一组糖尿病大鼠在OA攻击前2小时接受中性鱼精蛋白Hagedorn胰岛素（NPH，4 IU，s.c.）治疗。攻击后六小时，进行支气管肺泡灌洗（BAL）以释放介质，并且将肺组织匀浆用于信号通路的蛋白质印迹分析。结果：相对于非糖尿病大鼠，糖尿病大鼠的OA诱导的细胞外信号调节激酶（ERK，59％），p38（53％），蛋白激酶B（Akt，46％）磷酸化显着降低抗原攻击后，肺匀浆中的蛋白激酶C（PKC）-α（63％）和PKC-δ（38％）。在糖尿病大鼠中，NF-κBp65亚基的激活和IκBα的磷酸化几乎被抑制。还观察到肺匀浆中诱导型一氧化氮合酶（iNOS，32％）和环氧合酶-2（COX-2，46％）的表达降低。糖尿病大鼠中前列腺素（PG）-E_2，一氧化氮（NO）和白介素（IL）-6的BAL浓度降低（分别为74％，44％和65％），而细胞因子诱导的中性白细胞趋化因子（CINC） ）-2浓度与对照动物没有差异。用胰岛素治疗糖尿病大鼠可完全或部分恢复所有这些参数。该胰岛素治疗方案仅部分降低了血糖水平。结论：数据表明胰岛素在过敏性肺的早期调节MAPK，PI3K，PKC和NF-κB通路，诱导型酶iNOS和COX-2的表达以及NO，PGE_2和IL-6的水平。糖尿病大鼠发炎。建议胰岛素是过敏性刺激后细胞内信号最佳转导所必需的。

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