Nakayama Mieko, Inoguchi Toyoshi, Sonta Toshiyo, Maeda Yasutaka, Sasaki Shuji, Sawada Fumi, Tsubouchi Hirotaka, Sonoda Noriyuki, Kobayashi Kunihisa, Sumimoto Hideki, Nawata Hajime
Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Biochem Biophys Res Commun. 2005 Jul 15;332(4):927-33. doi: 10.1016/j.bbrc.2005.05.065.
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 1 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.
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所起的作用。免疫染色分析表明，与年龄匹配的对照相比，在2型糖尿病动物模型OLETF大鼠（60周龄）和db/db小鼠（14周龄）的胰岛中，NAD(P)H氧化酶成分gp91phox和p22phox的染色强度显著增加，这与氧化应激标志物8-羟基脱氧鸟苷或4-羟基-2-壬烯醛修饰蛋白水平的升高相关。在db/db小鼠中，口服血管紧张素II 1型受体拮抗剂缬沙坦（5 mg/kg）4周可显著减弱gp91phox和p22phox表达的增加，同时抑制氧化应激，并部分恢复胰岛中降低的胰岛素含量。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。该机制可能是预防β细胞损伤的新治疗靶点。
