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. 2025 Mar 3:24:339-350.
doi: 10.17179/excli2024-8051. eCollection 2025.

Long-term nitrate administration modulates sialin gene expression in the main tissues of male Wistar rats with type 2 diabetes

Sajad Jeddi  1 , Nasibeh Yousefzadeh  1 , Vajiheh Khorasani  1 , Maryam Zarkesh  2 , Khosrow Kashfi  3 , Asghar Ghasemi  1
Affiliations

Long-term nitrate administration modulates sialin gene expression in the main tissues of male Wistar rats with type 2 diabetes

Sajad Jeddi et al. EXCLI J. .

Abstract

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.

Keywords: nitrate; nitrate transporter; nitrite; sialin; type 2 diabetes.

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Figures

Table 1
Table 1. Primers sequence
Table 2
Table 2. Fasting serum glucose concentrations and body weights at the beginning and end of the study in type 2 diabetes (T2D) and T2D +nitrate rats.
Figure 1
Figure 1. Experimental design of the study. NO, Nitric oxide; HFD, High-fat diet; T2D, Type 2 diabetes; STZ, Streptozotocin
Figure 2
Figure 2. Changes in tissues' nitrate and nitrite levels in type 2 diabetes (T2D) and T2D+nitrate groups. NO, Nitric oxide
Figure 3
Figure 3. Changes in gene expression of sialin in type 2 diabetes (T2D) and T2D+nitrate groups
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