Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neurophysiology Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nitric Oxide. 2018 May 1;75:27-41. doi: 10.1016/j.niox.2018.02.002. Epub 2018 Feb 10.
Supplementation with inorganic nitrate to boost the nitrate-nitrite-nitric oxide (NO) pathway, may act as a potential therapeutic agent in diabetes. The aim of this study was to determine the effects of nitrate on carbohydrate metabolism, lipid profiles, oxidative stress, and inflammation in obese type 2 diabetic rats.
Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Diabetes was induced using a high-fat diet and low-dose of streptozotocin. Sodium nitrate (100 mg/L in drinking water) was administered simultaneously for two months. Serum levels of fasting glucose, insulin, and lipid profiles were measured every 2-weeks. Glycated hemoglobin (HbA1c) was measured monthly. Serum thiobarbituric reactive substances (TBARS) level and catalase activity were measured before and after treatment. At the end of the study, glucose, pyruvate, and insulin tolerance tests were done. Glucose-stimulated insulin secretion (GSIS) and insulin content from isolated pancreatic islets were also assessed; mRNA expression of iNOS as well as mRNA expression and protein levels of GLUT4 in insulin-sensitive tissues, and serum IL-1β were determined.
Nitrate supplementation in diabetic rats significantly improved glucose tolerance, lipid profiles, and catalase activity as well as decreased gluconeogenesis, fasting glucose, insulin, and IL-1β; although it had no significant effect on GSIS, islet insulin content, HbA1c, and serum TBARS. Compared to the controls, in diabetic rats, mRNA expression and protein levels of GLUT4 were significantly lower in the soleus muscle (54% and 34%, respectively) and epididymal adipose tissue (67% and 41%, respectively). In diabetic rats, nitrate administration increased GLUT4 mRNA expression and protein levels in both soleus muscle (215% and 17%, respectively) and epididymal adipose tissue (344% and 22%, respectively). In diabetic rats, nitrate significantly decreased elevated iNOS mRNA expression in both the soleus muscle and epididymal adipose tissue.
Chronic nitrate supplementation in obese type 2 diabetic rats improved glucose tolerance, insulin resistance, and dyslipidemia; these favorable effects were associated with increased mRNA and protein expression of GLUT4 and decreased mRNA expression of iNOS in insulin-sensitive tissues, and with decreased gluconeogenesis, inflammation, and oxidative stress.
补充无机硝酸盐以增强硝酸盐-亚硝酸盐-一氧化氮（NO）途径，可能成为糖尿病的一种潜在治疗药物。本研究旨在确定硝酸盐对肥胖 2 型糖尿病大鼠碳水化合物代谢、脂质谱、氧化应激和炎症的影响。
雄性 Wistar 大鼠分为 4 组：对照组、对照组+硝酸盐、糖尿病组和糖尿病+硝酸盐。糖尿病通过高脂肪饮食和低剂量链脲佐菌素诱导。同时在饮用水中添加 100mg/L 的硝酸钠，持续两个月。每两周测量一次空腹血糖、胰岛素和血脂水平。每月测量一次糖化血红蛋白（HbA1c）。在治疗前后测量血清硫代巴比妥酸反应物质（TBARS）水平和过氧化氢酶活性。研究结束时，进行葡萄糖、丙酮酸和胰岛素耐量试验。还评估了葡萄糖刺激的胰岛素分泌（GSIS）和分离胰岛的胰岛素含量；胰岛素敏感组织中诱导型一氧化氮合酶（iNOS）的 mRNA 表达以及 GLUT4 的 mRNA 表达和蛋白水平，以及血清白细胞介素-1β（IL-1β）。
糖尿病大鼠补充硝酸盐可显著改善葡萄糖耐量、脂质谱和过氧化氢酶活性，并降低糖异生、空腹血糖、胰岛素和 IL-1β；尽管它对 GSIS、胰岛胰岛素含量、HbA1c 和血清 TBARS 没有显著影响。与对照组相比，在糖尿病大鼠中，腓肠肌（分别降低 54%和 34%）和附睾脂肪组织（分别降低 67%和 41%）中 GLUT4 的 mRNA 表达和蛋白水平均显著降低。在糖尿病大鼠中，硝酸盐给药增加了腓肠肌（分别增加 215%和 17%）和附睾脂肪组织（分别增加 344%和 22%）中 GLUT4 的 mRNA 表达和蛋白水平。在糖尿病大鼠中，硝酸盐显著降低了腓肠肌和附睾脂肪组织中升高的 iNOS mRNA 表达。
在肥胖 2 型糖尿病大鼠中慢性补充硝酸盐可改善葡萄糖耐量、胰岛素抵抗和血脂异常；这些有利影响与胰岛素敏感组织中 GLUT4 的 mRNA 和蛋白表达增加以及 iNOS 的 mRNA 表达减少有关，与糖异生、炎症和氧化应激减少有关。
