Protection of Diabetic mellitus by Food Components

食品成分对糖尿病的保护

• 批准号: 08456066
• 负责人: OSAWA Toshihiko
• 金额: $ 4.93万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08456066/
• 关键词: diabetes; oxidative stress; Biomarker; methylglyoxal; Advanced Glycation End Products; Lemon flavonoids; メチルグリオキサール; 8-ヒドロキシデオキシグアノシン; カルボキメチルリジン; ULET-F; ストレプトゾトシン; グルタチオン

Recently, much attention has been focused on the relationship between the oxidative stress and diabetes. High glucose level causes glycation of proteins and also generation of reactive oxygen species (ROS) during the polyol metabolism, redox, prostagrandins metabolisms and autoxidation of glucose, and these ROS induce oxidative break down of the membrane polyunsaturated fatty acids is known to be acompanied by the formation of a complex mixture of lipidhydroperoxides and secondary products. We have been succeeded in isolationg a novel type of advanced glycation end products (AGEs), named MRX,which has been found to be produced by the reaction of glucose, arginine and cysteine. We have also suceeded in developing immunochemical evaluation methods for oxidative stress by application of polyclonal and monoclonal antibodies using lipidperoxide-modified proteins, carboxymethylisine and 8-hydroxy-deoxyguanosine (8-OH-dG) as an epitope. By detailed examination, it was found that a large quant ity of lipidhydroperoxides and 8-OH-dG was detected in urine excreted streptozotocin-induced diabetic rats, together with the changes of glutathione-related enzymes. lipidhydroperoxides and 8-OH-dG was also detected in urine excreted by OLETF,the mod l of naturally occuring diabetes mellitus (DM) type II of human. We have also found that lemon flavonoids have strong antioxidative protection in diabetic rat model induced by STZ.

近年来，氧化应激与糖尿病之间的关系受到广泛关注。高葡萄糖水平导致蛋白质糖化，并在多元醇代谢、氧化还原、前列腺素代谢和葡萄糖自氧化过程中产生活性氧（ROS），这些ROS诱导膜多不饱和脂肪酸的氧化分解，并伴随着脂质氢过氧化物和次级产物的复杂混合物的形成。我们成功分离出一种新型的晚期糖基化终末产物（AGEs），命名为MRX，它是由葡萄糖、精氨酸和半胱氨酸反应产生的。我们还成功地开发了氧化应激的免疫化学评估方法，通过应用多克隆和单克隆抗体，使用脂质过氧化物修饰蛋白、羧甲基丙氨酸和8-羟基-脱氧鸟苷(8-OH-dG)作为表位。经详细检查发现，链脲佐菌素诱发的糖尿病大鼠尿液中检出大量脂质过氧化氢和8-OH-dG，同时谷胱甘肽相关酶也发生变化。人类自然发生的 II 型糖尿病 (DM) 模型 OLETF 排出的尿液中也检测到脂质过氧化氢和 8-OH-dG。我们还发现柠檬黄酮类化合物对 STZ 诱导的糖尿病大鼠模型具有很强的抗氧化保护作用。

项目成果

Y.Kato他: "Immunochemical Detection of Carboxymethylated Apo B-100 in Copper-Oxidized LDL" Biochem.Biophys.Res.Commun.226. 923-927 (1996)

Y. Kato 等人：“铜氧化 LDL 中羧甲基化 Apo B-100 的免疫化学检测”Biochem.Biophys.Res.Commun.226 (1996)。

T.Osawa: "Lipid Peroxides and Related Free Radicals" Japan Scientific Society Press, 182 (1997)

T.Osawa：“脂质过氧化物和相关自由基”日本科学会出版社，182（1997）

Y.Kato.etc: "Oxidative Modification of Tryptophan Residues Exposed to Peroxynitrite" Biochem.Biophys.Res.Commun.234. 82-84 (1997)

Y.Kato.等：“暴露于过氧亚硝酸盐的色氨酸残基的氧化修饰”Biochem.Biophys.Res.Commun.234。

S.Toyokuni 他: "Quantitative Immunohistochemical Determination of 8-Hydraxy-z'-Deoxyguanosine by a Monoclonal Antibody N45 1 : Its Application of Ferric Nitrilotriacetate-Induced Renal Corcinogenesis Model" Laboratory Investigation. 76(3). 365-374 (1997)

S.Toyokuni 等人：“单克隆抗体 N45 定量免疫组织化学测定 8-Hydraxy-z-脱氧鸟苷：其在次氮基三乙酸铁诱导的肾癌发生模型中的应用”实验室研究 76(3)。 1997）

Y.Miyake, etc: "Isolation of Eriocitrin (Eriodictyol 7-rutinoside) from Lemon Fruit (Citrus limon BURM.f) and Its Antioxidative" Food Sci.Technol.Int.Tokyo. 3 (1). 84-89 (1997)

Y.Miyake等：“从柠檬果实（Citrus limon BURM.f）中分离圣草次苷（Eriodictyol 7-rutinoside）及其抗氧化作用”Food Sci.Technol.Int.Tokyo。