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

Authors

  • Sajad Jeddi Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-3911-6620
  • Nasibeh Yousefzadeh Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0001-8592-2124
  • Vajiheh Khorasany Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0009-0004-8353-3685
  • Maryam Zarkesh Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-8519-4865
  • Khosrow Kashfi Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, NY, USA https://orcid.org/0000-0002-4060-7283
  • Asghar Ghasemi Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran, No. 24, Arabi Street, Daneshjoo Blvd, Velenjak, P.O. Box: 19395-4763, Tehran, Iran. Phone: +98 21 22409309, Fax: +98 21 22416264, E-mail: Ghasemi@endocrine.ac.ir https://orcid.org/0000-0001-6867-2151

DOI:

https://doi.org/10.17179/excli2024-8051

Keywords:

sialin, nitrite, nitrate, type 2 diabetes, nitrate transporter

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.

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Published

2025-03-03

How to Cite

Jeddi, S., Yousefzadeh, N., Khorasany, V., Zarkesh, M., Kashfi, K., & Ghasemi, A. (2025). Long-term nitrate administration modulates sialin gene expression in the main tissues of male Wistar rats with type 2 diabetes. EXCLI Journal, 24, 339–350. https://doi.org/10.17179/excli2024-8051

Issue

Vol. 24 (2025)

Section

Original articles

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Copyright (c) 2025 Sajad Jeddi, Nasibeh Yousefzadeh, Vajiheh Khorasany, Maryam Zarkesh, Khosrow Kashfi, Asghar Ghasemi

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