Ghasemi Asghar, Gheibi Sevda, Kashfi Khosrow, Jeddi Sajad
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Clinical Sciences in Malmö, Unit of Molecular Metabolism, Lund University Diabetes Center, Clinical Research Center, Lund University, Malmö, Sweden.
Iran J Basic Med Sci. 2023 Apr;26(4):420-428. doi: 10.22038/IJBMS.2023.68245.14900.
Nitrite, a nitric oxide (NO) donor, increases insulin secretion from pancreatic islets and has positive metabolic effects in type 2 diabetes (T2D). Here, we test the hypothesis of whether nitrite-induced insulin secretion is due to blunting of diabetes-induced oxidative stress in the islets.
T2D was created in male rats using a combination of streptozotocin at 25 mg/kg and a high-fat diet. Wistar rats were assigned to 3 groups (n=6 in each group), including control, T2D, and T2D+nitrite; the latter group consumed drinking water containing sodium nitrite (50 mg/l) for eight weeks. At the end of the study, mRNA levels of NADPH oxidase (Nox1, 2, 3, and 4), superoxide dismutase (SOD1, 2, and 3), glutathione peroxides (GPX1 and 7), glutathione reductase (GR), catalase, thioredoxin (TXN1 and 2), and thioredoxin reductase (TXNRD1) were measured in the isolated pancreatic islets.
In the islets of diabetic rats, mRNA expressions of Nox1, 2, and 4 were higher, whereas expressions of SOD1, 2, catalase, GPX1, 7, GR, and TXN1 were lower than controls. Nitrite significantly (all -values<0.05) decreased gene expression of Nox1 (0.39-fold) and Nox4 (0.23-fold) and increased gene expression of SOD1 (2.2-fold), SOD2 (2.8-fold), catalase (2.7-fold), GPX1 (2.2-fold), GPX7 (6.0-fold), GR (3.0-fold), TXN1 (2.1-fold), and TXNRD1 (2.3-fold) in diabetic rats.
Nitrite decreased oxidative stress in isolated pancreatic islets of rats with T2D by suppressing oxidants and augmenting anti-oxidants. These findings favor the notion that nitrite-induced insulin secretion is partially due to decreased oxidative stress.
亚硝酸盐作为一种一氧化氮（NO）供体，可增加胰岛的胰岛素分泌，并对2型糖尿病（T2D）具有积极的代谢作用。在此，我们检验亚硝酸盐诱导的胰岛素分泌是否归因于胰岛中糖尿病诱导的氧化应激减弱这一假设。
使用25mg/kg链脲佐菌素和高脂饮食联合诱导雄性大鼠患T2D。将Wistar大鼠分为3组（每组n = 6），包括对照组、T2D组和T2D + 亚硝酸盐组；后一组饮用含亚硝酸钠（50mg/l）的饮用水八周。在研究结束时，测定分离的胰岛中NADPH氧化酶（Nox1、2、3和4）、超氧化物歧化酶（SOD1、2和3）、谷胱甘肽过氧化物酶（GPX1和7）、谷胱甘肽还原酶（GR）、过氧化氢酶、硫氧还蛋白（TXN1和2）以及硫氧还蛋白还原酶（TXNRD1）的mRNA水平。
在糖尿病大鼠的胰岛中，Nox1、2和4的mRNA表达较高，而SOD1、2、过氧化氢酶、GPX1、7、GR和TXN1的表达低于对照组。亚硝酸盐显著（所有P值<0.05）降低糖尿病大鼠中Nox1（0.39倍）和Nox4（0.23倍）的基因表达，并增加SOD1（2.2倍）、SOD2（2.
