Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist
Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist
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DOI：
10.1016/j.bbrc.2005.05.065
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发表时间：
2005-07-15
影响因子：
3.1
通讯作者：
Nawata, H
中科院分区：
文献类型：
--
作者：
Nakayama, M;Inoguchi, T;Nawata, H
本研究旨在揭示NAD（P）H氧化酶在2型糖尿病胰岛氧化应激增加中的作用。免疫组化分析显示，2型糖尿病动物模型OLETF大鼠胰岛中NAD（P）H氧化酶组分gp 91 phox和p22 phox的染色强度显著增加（60周龄）和db/db小鼠（14周龄），分别与年龄匹配的对照组相比，与氧化应激标志物水平增加相关，8-羟基-脱氧鸟苷或4-羟基-2-壬烯醛修饰的蛋白质。在db/db小鼠中，口服血管紧张素II I型受体拮抗剂缬沙坦（5 mg/kg）4周显著减弱了gp 91 phox和p22 phox表达的增加，同时抑制了氧化应激，并部分恢复了胰岛中胰岛素含量的下降。血管紧张素II相关的NAD（P）H氧化酶表达增加可能在2型糖尿病胰岛氧化应激增加中起重要作用。这一机制可能是预防β细胞损伤的一个新的治疗靶点。(c)2005年爱思唯尔公司All rights reserved.
This study was undertaken to reveal the role of NAD(P)H oxidase in increased oxidative stress in islets of Type 2 diabetes. Immunostaining analysis showed that staining intensities of NAD(P)H oxidase components, gp91phox and p22phox, significantly increased in islets of animal models of Type 2 diabetes, OLETF rats (60 weeks of age) and db/db mice (14 weeks of age), compared with age-matched controls, respectively, correlating with increased levels of oxidative stress marker, 8-hydroxy-deoxyguanosine or 4-hydroxy-2-nonenal modified protein. In db/db mice, oral administration of angiotensin II Type I receptor antagonist valsartan (5 mg/kg) for 4 weeks significantly attenuated the increased expression of gp91phox and p22phox together with inhibition of oxidative stress and partially restored decreased insulin contents in islets. Angiotensin II-related increased expression of NAD(P)H oxidase may play an important role in increased oxidative stress in islets of Type 2 diabetes. This mechanism may be a novel therapeutic target for preventing beta-cell damage. (c) 2005 Elsevier Inc. All rights reserved.