Angiotensin II shifts insulin signaling into vascular remodeling from glucose metabolism in vascular smooth muscle cells.
Angiotensin II shifts insulin signaling into vascular remodeling from glucose metabolism in vascular smooth muscle cells.
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DOI：
10.1038/ajh.2011.114
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发表时间：
2011-10
影响因子：
3.2
通讯作者：
Nishiyama, Akira
中科院分区：
文献类型：
--
作者：
Hitomi, Hirofumi;Kaifu, Kumiko;Fujita, Yoshiko;Sofue, Tadashi;Nakano, Daisuke;Moriwaki, Kumiko;Hara, Taiga;Kiyomoto, Hideyasu;Kohno, Masakazu;Kobori, Hiroyuki;Nishiyama, Akira
关键词：
为了阐明血管紧张素II（Ang II）在胰岛素诱导的动脉硬化中的作用，我们研究了Ang II对胰岛素诱导的大鼠血管平滑肌细胞（VSMCs）有丝分裂原活化蛋白（MAP）激酶激活和细胞肥大的影响。蛋白质印迹法检测磷酸化MAP激酶。细胞肥大和葡萄糖摄取从[3 H]-标记的亮氨酸和-脱氧-D-葡萄糖的掺入，分别进行了评价。通过库尔特计数器测量细胞大小。而血管紧张素Ⅱ（100 nmol/l，18小时）增加细胞肥大的胰岛素（10 nmol/l，24小时），胰岛素单独没有影响肥大没有血管紧张素Ⅱ预处理。胰岛素增加p38 MAP激酶和c-Jun N-末端激酶（JNK）的磷酸化;在Ang II的存在下，p38 MAP激酶和JNK被胰岛素进一步激活。p38 MAP激酶抑制剂SB 203580（10 μmol/l）和JNK抑制剂SP 600125（20 μmol/l）可阻断Ang II存在时胰岛素对[3 H]-亮氨酸的掺入。Ang II受体阻断剂RNH-6270（100 nmol/l）和抗氧化剂ebselen（40 μmol/l）均抑制血管细胞肥大。特异性消耗胰岛素受体底物-1与小干扰RNA增加[3 H]-亮氨酸掺入胰岛素（10 nmol/l，24小时）;预处理与血管紧张素II减弱胰岛素（10 nmol/l，30分钟）诱导的葡萄糖摄取。血管紧张素II通过氧化应激和MAP激酶介导的途径减弱胰岛素刺激的葡萄糖摄取并增强血管平滑肌细胞肥大血管紧张素II还可能导致胰岛素信号从葡萄糖代谢转向血管重塑，影响高血压中胰岛素诱导的动脉硬化。
To clarify the role of angiotensin II (Ang II) in insulin-induced arteriosclerosis, we examined the effects of Ang II on insulin-induced mitogen-activated protein (MAP) kinase activation and cellular hypertrophy in rat vascular smooth muscle cells (VSMCs). Phosphorylated MAP kinases were detected with western blot analysis. Cellular hypertrophy and glucose uptake were evaluated from incorporation of [3H]-labeled-leucine and -deoxy-D-glucose, respectively. Cell sizes were measured by Coulter counter. While Ang II (100 nmol/l, 18 h) augmented cellular hypertrophy by insulin (10 nmol/l, 24 h), insulin alone did not affect hypertrophy without Ang II pretreatment. Insulin increased p38MAP kinase and c-Jun N-terminal kinase (JNK) phosphorylation; in the presence of Ang II, p38MAP kinase, and JNK were further activated by insulin. Treatment of a p38MAP kinase inhibitor, SB203580 (10 μmol/l), and a JNK inhibitor, SP600125 (20 μmol/l), abrogated the [3H]-leucine incorporation by insulin in the presence of Ang II. Both the Ang II receptor blocker, RNH-6270 (100 nmol/l), and an antioxidant, ebselen (40 μmol/l), inhibited vascular cell hypertrophy. Specific depletion of insulin receptor substrate-1 with small interfering RNA increased [3H]-leucine incorporation by insulin (10 nmol/l, 24 h); pretreatment with Ang II attenuated insulin (10 nmol/l, 30 min)-induced glucose uptake. Ang II attenuates insulin-stimulated glucose uptake and enhances vascular cell hypertrophy via oxidative stress- and MAP kinase-mediated pathways in VSMCs. Ang II may also cause insulin signaling to diverge from glucose metabolism into vascular remodeling, affecting insulin-induced arteriosclerosis in hypertension.
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影响因子：
13.6
作者：
Miyata, K;Rahman, M;Nishiyama, A
通讯作者：
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影响因子：
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STOLAR, MW
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