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.

中文翻译：

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长期共同施用亚硝酸钠和氢硫化钠抑制雄性2型糖尿病大鼠的肝糖异生：PI3K-Akt-eNOS途径的作用

目的

硫化氢（H ₂ S）和一氧化氮（NO）的缺乏会导致2型糖尿病（T2D）的发展。曾有报道称，亚硝酸钠和硫化氢钠（NaSH）并用对T2D大鼠有抑制肝糖异生的作用。然而，尚未阐明其基本机制。这项研究的目的是确定亚硝酸钠和NaSH共同给药对T2D大鼠肝糖异生相关基因表达的长期影响。

方法

使用高脂饮食和低剂量链脲佐菌素（30 mg / kg）诱导T2D。大鼠分为5组（n  = 7 /组）：对照组，T2D，T2D +亚硝酸盐，T2D + NaSH和T2D +亚硝酸盐+ NaSH。施用亚硝酸盐（50 mg / L）和NaSH（0.28 mg / kg）9周。在第九周结束时进行腹膜丙酮酸耐受性试验（PTT），并测量肝脏中PI3K，Akt，eNOS，PEPCK，G6Pase和FBPase的mRNA表达。

结果

亚硝酸盐和NaSH共同给药可降低PTT期间升高的血清葡萄糖浓度。与T2D +亚硝酸盐相比，亚硝酸盐和NaSH的共同给药导致PI3K，Akt和eNOS的mRNA表达显着增加，而G6Pase和FBPase的mRNA表达则显着下降，但对PEPCK表达没有影响。

结论

长期低剂量NaSH给药可增强亚硝酸盐对T2D大鼠肝脏关键肝糖异生酶mRNA表达的抑制作用。亚硝酸盐和NaSH共同给药对糖异生的这种抑制作用与肝脏中PI3K，Akt和eNOS的基因表达增加有关。