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Long-term co-administration of sodium nitrite and sodium hydrosulfide inhibits hepatic gluconeogenesis in male type 2 diabetic rats : Role of PI3K-Akt-eNOS pathway

Jeddi, Sajad ; Gheibi, Sevda LU ; Carlström, Mattias ; Kashfi, Khosrow and Ghasemi, Asghar (2021) In Life Sciences 265.
Abstract

Objective: A deficiency in hydrogen sulfide (H2S) and nitric oxide (NO) contributes to the development of type 2 diabetes (T2D). An inhibitory effect on liver gluconeogenesis has been reported in rats with T2D with co-administration of sodium nitrite and sodium hydrosulfide (NaSH); the underlying mechanisms have however not yet been elucidated. The aim of this study is to determine the long-term effects of co-administering sodium nitrite and NaSH on expression of genes involved in liver gluconeogenesis in rats with T2D. Methods: T2D was induced using a high fat diet combined with low-dose of streptozotocin (30 mg/kg). Rats were divided into 5 groups (n = 7/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D +... (More)

Objective: A deficiency in hydrogen sulfide (H2S) and nitric oxide (NO) contributes to the development of type 2 diabetes (T2D). An inhibitory effect on liver gluconeogenesis has been reported in rats with T2D with co-administration of sodium nitrite and sodium hydrosulfide (NaSH); the underlying mechanisms have however not yet been elucidated. The aim of this study is to determine the long-term effects of co-administering sodium nitrite and NaSH on expression of genes involved in liver gluconeogenesis in rats with T2D. Methods: T2D was induced using a high fat diet combined with low-dose of streptozotocin (30 mg/kg). Rats were divided into 5 groups (n = 7/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite+NaSH. Nitrite (50 mg/L) and NaSH (0.28 mg/kg) were administered for 9 weeks. Intraperitoneal pyruvate tolerance test (PTT) was performed at the end of the ninth week and mRNA expressions of PI3K, Akt, eNOS, PEPCK, G6Pase, and FBPase were measured in the liver. Results: Co-administration of nitrite and NaSH decreased elevated serum glucose concentrations during PTT. Compared to T2D + nitrite, co-administration of nitrite and NaSH resulted in significant increases in mRNA expression of PI3K, Akt, and eNOS and significant decreases in mRNA expression of G6Pase and FBPase but had no effect on PEPCK expression. Conclusion: Long-term NaSH administration at low-dose, potentiated the inhibitory effects of nitrite on mRNA expression of key liver gluconeogenic enzymes in rats with T2D. This inhibitory effect of nitrite and NaSH co-administration on gluconeogenesis were associated with increased gene expression of PI3K, Akt, and eNOS in the liver.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gene expression, Gluconeogenesis, Liver, Nitrite, Rat, Type 2 diabetes
in
Life Sciences
volume
265
article number
118770
publisher
Elsevier
external identifiers
  • pmid:33212150
  • scopus:85096400475
ISSN
0024-3205
DOI
10.1016/j.lfs.2020.118770
language
English
LU publication?
yes
id
9f27180b-d375-4679-bd5e-9d02e448c9ee
date added to LUP
2020-12-02 07:41:21
date last changed
2024-06-13 01:03:31
@article{9f27180b-d375-4679-bd5e-9d02e448c9ee,
  abstract     = {{<p>Objective: A deficiency in hydrogen sulfide (H<sub>2</sub>S) and nitric oxide (NO) contributes to the development of type 2 diabetes (T2D). An inhibitory effect on liver gluconeogenesis has been reported in rats with T2D with co-administration of sodium nitrite and sodium hydrosulfide (NaSH); the underlying mechanisms have however not yet been elucidated. The aim of this study is to determine the long-term effects of co-administering sodium nitrite and NaSH on expression of genes involved in liver gluconeogenesis in rats with T2D. Methods: T2D was induced using a high fat diet combined with low-dose of streptozotocin (30 mg/kg). Rats were divided into 5 groups (n = 7/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite+NaSH. Nitrite (50 mg/L) and NaSH (0.28 mg/kg) were administered for 9 weeks. Intraperitoneal pyruvate tolerance test (PTT) was performed at the end of the ninth week and mRNA expressions of PI3K, Akt, eNOS, PEPCK, G6Pase, and FBPase were measured in the liver. Results: Co-administration of nitrite and NaSH decreased elevated serum glucose concentrations during PTT. Compared to T2D + nitrite, co-administration of nitrite and NaSH resulted in significant increases in mRNA expression of PI3K, Akt, and eNOS and significant decreases in mRNA expression of G6Pase and FBPase but had no effect on PEPCK expression. Conclusion: Long-term NaSH administration at low-dose, potentiated the inhibitory effects of nitrite on mRNA expression of key liver gluconeogenic enzymes in rats with T2D. This inhibitory effect of nitrite and NaSH co-administration on gluconeogenesis were associated with increased gene expression of PI3K, Akt, and eNOS in the liver.</p>}},
  author       = {{Jeddi, Sajad and Gheibi, Sevda and Carlström, Mattias and Kashfi, Khosrow and Ghasemi, Asghar}},
  issn         = {{0024-3205}},
  keywords     = {{Gene expression; Gluconeogenesis; Liver; Nitrite; Rat; Type 2 diabetes}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Elsevier}},
  series       = {{Life Sciences}},
  title        = {{Long-term co-administration of sodium nitrite and sodium hydrosulfide inhibits hepatic gluconeogenesis in male type 2 diabetic rats : Role of PI3K-Akt-eNOS pathway}},
  url          = {{http://dx.doi.org/10.1016/j.lfs.2020.118770}},
  doi          = {{10.1016/j.lfs.2020.118770}},
  volume       = {{265}},
  year         = {{2021}},
}