Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats
Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats
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DOI：
10.1097/hjh.0b013e32832c419a
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Ito, Sadayoshi
中科院分区：
文献类型：
--
作者：
Guo, Qi;Mori, Takefumi;Ito, Sadayoshi
目的糖酵解代谢产物甲基乙醛可能在糖尿病和高血压的发生发展中起重要作用，但其确切机制尚未完全阐明。方法将SD大鼠随机分为4组：对照组(正常饮水)、1%甲基乙二醛+N-乙酰半胱氨酸(NAC)(800 mg/kg/d)和糖基化终末产物(AGEs)抑制剂TM2002(100 mg/kg/d)。治疗4周后，采用正常血糖、高胰岛素葡萄糖钳夹技术评价胰岛素抵抗。在另一组大鼠中，单独给予高盐饮食(4%)，在饮用水中加入1%甲基乙二醛的标准饲料，或高盐饮食+甲基乙二醛，为期4周。用免疫组织化学方法检测硝基酪氨酸和乙二醛诱导的肾脏AGEs和N-epsilon-羧乙基-赖氨酸(CEL)。结果NAC和TM2002治疗4周后，大鼠胰岛素抵抗得到完全改善。与单独给予甲基乙醛或高盐饮食相比，联合给予甲基乙二醛和高盐饮食显著增加了小鼠的收缩压、尿白蛋白排泄、尿硫代巴比妥酸反应物质排泄和肾脏硝基酪氨酸的表达(氧化应激的标志)。与非甲基乙醛处理组大鼠相比，甲基乙二醛处理组大鼠肾脏CEL显著增加。结论甲基乙醛诱导的胰岛素抵抗和盐敏感性至少部分是通过增加氧化应激和/或AGEs的形成而实现的。本研究进一步证明了乙二醛是胰岛素抵抗和盐敏感型高血压发病机制中的致病因素之一。J Hyperten 27：1664-1671(C)2009 Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins。
Objectives Methylglyoxal, a metabolite of the glycolysis pathway, may play an important role in the development of diabetes and hypertension, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether methylglyoxal could directly induce insulin resistance and salt sensitivity in Sprague-Dawley rats.Methods Rats were allocated to four groups: control (normal drinking water), 1% methylglyoxal in drinking water, 1% methylglyoxal plus N-acetyl cysteine (NAC) (800 mg/kg per day), a methylglyoxal scavenger, or TM2002 (100 mg/kg per day), an advanced glycation endproducts (AGEs) inhibitor. After 4-week treatment insulin resistance was evaluated by an euglycemic hyperinsulinemic glucose clamp technique. In another set of rats, either a high-salt diet (4%) alone, standard rat chow with 1% methylglyoxal in drinking water or high-salt diet plus methylglyoxal was given for 4 weeks. Immunohistochemistry was performed to measure nitrotyrosine and methylglyoxal-induced AGEs, N-epsilon-carboxyethyl-lysine (CEL) in the kidney.Results Four-week treatment with NAC or TM2002 completely improved methylglyoxal-induced insulin resistance. Co-administration of methylglyoxal and high-salt diet significantly increased systolic blood pressure, urinary albumin excretion, urinary thiobarbituric acid-reactive substances excretion and the renal nitrotyrosine expression in the kidney (markers of oxidative stress)compared with methylglyoxal or high-salt diet alone. Renal CEL was significantly increased in methylglyoxal-treated rats compared with nonmethylglyoxal-treated rats.Conclusion These results indicate that methylglyoxal-induced insulin resistance and salt sensitivity at least in part by increasing oxidative stress and/or AGEs formation in Sprague-Dawley rats. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of insulin resistance and salt-sensitive hypertension. J Hypertens 27: 1664-1671 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.