Lack of inducible nitric oxide synthase does not prevent aging-associated insulin resistance
Lack of inducible nitric oxide synthase does not prevent aging-associated insulin resistance
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DOI：
10.1016/j.exger.2010.05.004
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发表时间：
2010-09-01
影响因子：
3.9
通讯作者：
Park, So-Young
中科院分区：
文献类型：
--
作者：
Cha, Hye-Na;Kim, Yong-Woon;Park, So-Young
诱导型一氧化氮合酶 (iNOS) 参与肥胖引起的胰岛素抵抗。由于衰老伴随着 iNOS 表达增加，因此使用高胰岛素-正常血糖钳在 7 个月大（成人）和 22 个月大（老年） iNOS 敲除小鼠和野生型小鼠中研究了 iNOS 基因缺失对衰老相关胰岛素抵抗的影响。虽然野生型小鼠的体重和脂肪量增加，但肌肉质量随着衰老而减少。然而，由于运动活动增加，iNOS 敲除小鼠的身体成分并没有随着年龄的增长而改变。在野生型小鼠中，血浆中的一氧化氮代谢物以及骨骼肌中的诱导一氧化氮合酶和硝基酪氨酸的蛋白质水平随着年龄的增长而增加。在 iNOS 基因敲除小鼠中，iNOS 基因的缺失会随着年龄的增长而减弱 NO 代谢物和硝基酪氨酸。野生型和 iNOS 敲除小鼠的全身和骨骼肌葡萄糖摄取均随着年龄的增长而减少，但两组之间没有差异。两组中肿瘤坏死因子-et 的血浆水平和外周组织中促炎细胞因子的基因表达均随着年龄的增长而增加，并且在 iNOS 敲除小鼠中更为明显。这些结果表明，iNOS 的缺乏并不能阻止小鼠与衰老相关的胰岛素抵抗，并且可能与促炎细胞因子的产生增加有关。 (C) 2010 Elsevier Inc. 保留所有权利。
Inducible nitric oxide synthase (iNOS) is involved in obesity-induced insulin resistance. Since aging is accompanied by increased iNOS expression, the effect of iNOS gene deletion on aging-associated insulin resistance was investigated in 7-month-old (adult) and 22-month-old (old) iNOS knockout and wild-type mice using the hyperinsulinemic-euglycemic clamp. While body weight and fat mass were increased, muscle mass was reduced with aging in wild-type mice. However, body composition was not changed with aging in iNOS knockout mice due to increased locomotor activity. NO metabolites in plasma, and protein levels of iNOS and nitrotyrosine in skeletal muscle increased with aging in wild-type mice. Deletion of iNOS gene attenuated NO metabolites and nitrotyrosine with aging in iNOS knockout mice. Glucose uptake in whole body and skeletal muscle was reduced with aging in both wild-type and iNOS knockout mice and there was no difference between two groups. Plasma level of tumor necrosis factor-et and gene expression of proinflammatory cytokines in peripheral tissues were increased with aging in both groups, and that was more heightened in iNOS knockout mice. These results suggest that lack of iNOS does not prevent aging-associated insulin resistance in mice and heightened production of proinflammatory cytokines may be involved. (C) 2010 Elsevier Inc. All rights reserved.