Jeddi Sajad, Yousefzadeh Nasibeh, Khorasani Vajiheh, Zarkesh Maryam, Kashfi Khosrow, Ghasemi Asghar
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
EXCLI J. 2025 Mar 3;24:339-350. doi: 10.17179/excli2024-8051. eCollection 2025.
The increased sialin gene expression in the main tissues of diabetic rats is associated with decreased nitrate and nitrite levels, suggesting a counterregulatory response for reduced nitric oxide (NO) bioavailability. In this study, we hypothesized that long-term nitrate administration (6 months) would decrease sialin gene expression in rats with type 2 diabetes (T2D). Rats were assigned to two groups (n=10): T2D and T2D+nitrate, receiving nitrate in their drinking water at a concentration of 100 mg/L over 6 months. Samples from the main tissues were collected and used to measure the gene expression of sialin, as well as nitrate and nitrite levels. Nitrate-treated T2D rats had higher nitrate levels in the soleus muscle (SM) (163 %), stomach (83 %), lung (271 %), pancreas (90 %), aorta (61 %), adrenal gland (88 %), brain (145 %), liver (95 %), and heart (87 %). Nitrite levels were also higher in SM (136 %), lung (108 %), pancreas (86 %), kidney (88 %), aorta (33 %), brain (221 %), epididymal adipose tissue (eAT) (52 %), and heart (93 %), of nitrate treated T2D rats (all P<0.05). Nitrate decreased sialin gene expression in the SM (0.21-fold, P<0.001), stomach (0.37-fold, P=0.002), liver (0.21-fold, P<0.001), and eAT (0.47-fold, P=0.016) but it increased it in the intestine (1.99-fold, P<0.001), pancreas (2.01-fold, P=0.006), and the kidney (2.45-fold, P<0.001) of diabetic rats, with no effects in the lung, aorta, adrenal gland, brain, and heart. Nitrate administration restores the compensatory increase in sialin gene expression in tissues of T2D rats. However, this compensatory mechanism is not generalizable to all tissues.
糖尿病大鼠主要组织中唾液酸转运蛋白基因表达增加与硝酸盐和亚硝酸盐水平降低有关,提示对一氧化氮(NO)生物利用度降低的一种反调节反应。在本研究中,我们假设长期给予硝酸盐(6个月)会降低2型糖尿病(T2D)大鼠的唾液酸转运蛋白基因表达。将大鼠分为两组(n = 10):T2D组和T2D + 硝酸盐组,T2D + 硝酸盐组大鼠在6个月内饮用含100 mg/L硝酸盐的水。收集主要组织的样本,用于测量唾液酸转运蛋白的基因表达以及硝酸盐和亚硝酸盐水平。接受硝酸盐处理的T2D大鼠的比目鱼肌(SM)(163%)、胃(83%)、肺(271%)、胰腺(90%)、主动脉(61%)、肾上腺(88%)、脑(145%)、肝(95%)和心脏(87%)中的硝酸盐水平较高。接受硝酸盐处理的T2D大鼠的SM(136%)、肺(108%)、胰腺(86%)、肾(88%)、主动脉(33%)、脑(221%)、附睾脂肪组织(eAT)(52%)和心脏(93%)中的亚硝酸盐水平也较高(所有P < 0.05)。硝酸盐降低了糖尿病大鼠SM(0.21倍,P < 0.001)、胃(0.37倍,P = 0.002)、肝(0.21倍,P < 0.001)和eAT(0.47倍,P = 0.016)中的唾液酸转运蛋白基因表达,但增加了肠道(1.99倍,P < 0.001)、胰腺(2.01倍,P = 0.006)和肾(2.45倍,P < 0.001)中的表达,对肺、主动脉、肾上腺、脑和心脏无影响。给予硝酸盐可恢复T2D大鼠组织中唾液酸转运蛋白基因表达的代偿性增加。然而,这种代偿机制并非适用于所有组织。