Gheibi Sevda, Bakhtiarzadeh Fatemeh, Jeddi Sajad, Farrokhfall Khadijeh, Zardooz Homeira, Ghasemi Asghar
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.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nitric Oxide. 2017 Apr 1;64:39-51. doi: 10.1016/j.niox.2017.01.003. Epub 2017 Jan 9.
Reduced bioavailability of nitric oxide (NO) is associated with pathogenesis of type 2 diabetes. Nitrite can act as a substrate for generation of systemic NO. The aim of this study was to examine the effects of nitrite administration on glucose-stimulated insulin secretion (GSIS) and islet insulin content in obese type 2 diabetic rats.
Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 8 weeks. Diabetes was induced using high-fat diet and low-dose of streptozotocine. Serum levels of fasting glucose, insulin, and lipid profile were measured and the insulin resistance/sensitivity indices were calculated every 2 weeks. Glycated hemoglobin (HbA) was measured every month. At the end of the study, tissue levels of glucose transporter 4 (GLUT4) protein and serum interleukin-1 beta (IL-1β) were measured as well as glucose and insulin tolerance test were done. GSIS from isolated pancreatic islets and islet insulin content were also determined.
Nitrite administration significantly increased insulin secretion in both control and diabetic rats in presence of 16.7 mM glucose. Nitrite also significantly increased islet insulin content by 27% and 39% in both control and diabetic rats, respectively. Nitrite decreased elevated serum IL-1β in diabetic rats (4.0 ± 0.2 vs. 2.9 ± 0.2 pg/mL, P = 0.001). In diabetic rats, nitrite also significantly increased tissue levels of GLUT4 by 22% and 26% in soleus muscle and epididymal adipose tissue, respectively. In addition, nitrite significantly improved glucose and insulin tolerance, insulin sensitivity, lipid profile, and decreased fasting glucose and insulin, but had no effect on HbA.
Long-term nitrite administration increased both insulin secretion and insulin content in obese type 2 diabetic rats. In addition, nitrite therapy had favorable effects on glucose tolerance, insulin resistance, inflammation, and dyslipidemia in type 2 diabetic rats.
一氧化氮（NO）生物利用度降低与2型糖尿病的发病机制有关。亚硝酸盐可作为全身NO生成的底物。本研究旨在探讨给予亚硝酸盐对肥胖2型糖尿病大鼠葡萄糖刺激的胰岛素分泌（GSIS）和胰岛胰岛素含量的影响。
雄性大鼠分为4组：对照组、对照组+亚硝酸盐组、糖尿病组和糖尿病+亚硝酸盐组。给予亚硝酸钠（饮用水中50mg/L）8周。采用高脂饮食和低剂量链脲佐菌素诱导糖尿病。每2周测量空腹血糖、胰岛素和血脂水平，并计算胰岛素抵抗/敏感性指数。每月测量糖化血红蛋白（HbA）。在研究结束时，测量葡萄糖转运蛋白4（GLUT4）蛋白的组织水平和血清白细胞介素-1β（IL-1β），并进行葡萄糖和胰岛素耐量试验。还测定了分离胰岛的GSIS和胰岛胰岛素含量。
在16.7mM葡萄糖存在下，给予亚硝酸盐显著增加了对照组和糖尿病大鼠的胰岛素分泌。亚硝酸盐还分别使对照组和糖尿病大鼠的胰岛胰岛素含量显著增加27%和39%。亚硝酸盐降低了糖尿病大鼠升高的血清IL-1β水平（4.0±0.2 vs.2.9±0.2pg/mL，P=0.001）。在糖尿病大鼠中，亚硝酸盐还分别使比目鱼肌和附睾脂肪组织中GLUT4的组织水平显著增加22%和26%。此外，亚硝酸盐显著改善了葡萄糖和胰岛素耐量、胰岛素敏感性、血脂谱，降低了空腹血糖和胰岛素，但对HbA无影响。
长期给予亚硝酸盐可增加肥胖2型糖尿病大鼠的胰岛素分泌和胰岛素含量。此外，亚硝酸盐治疗对2型糖尿病大鼠的葡萄糖耐量、胰岛素抵抗、炎症和血脂异常有有益影响。
