Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Clinical Sciences in Malmö, Unit of Molecular Metabolism, Lund University Diabetes Centre, Clinical Research Center, Malmö University Hospital, Lund University, Malmö, Sweden.
Life Sci. 2021 Jan 15;265:118770. doi: 10.1016/j.lfs.2020.118770. Epub 2020 Nov 16.
A deficiency in hydrogen sulfide (HS) 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.
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.
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.
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.
硫化氢（HS）和一氧化氮（NO）的缺乏会导致 2 型糖尿病（T2D）的发生。有报道称，在给予亚硝酸钠和硫氢化钠（NaSH）的 T2D 大鼠中，肝糖异生受到抑制；但潜在机制尚未阐明。本研究旨在确定长期给予亚硝酸钠和 NaSH 对 T2D 大鼠肝糖异生相关基因表达的影响。
采用高脂肪饮食联合小剂量链脲佐菌素（30mg/kg）诱导 T2D。将大鼠分为 5 组（n=7/组）：对照组、T2D 组、T2D+亚硝酸盐组、T2D+NaSH 组和 T2D+亚硝酸盐+NaSH 组。给予亚硝酸钠（50mg/L）和 NaSH（0.28mg/kg）9 周。第 9 周末行腹腔内丙酮酸耐量试验（PTT），检测各组大鼠血糖水平，检测大鼠肝组织中 PI3K、Akt、eNOS、PEPCK、G6Pase 和 FBPase 的 mRNA 表达。
与 T2D+亚硝酸盐组相比，亚硝酸钠和 NaSH 联合给药可降低 PTT 时升高的血清葡萄糖浓度，同时显著增加 PI3K、Akt 和 eNOS 的 mRNA 表达，显著降低 G6Pase 和 FBPase 的 mRNA 表达，但对 PEPCK 表达无影响。
长期低剂量 NaSH 给药可增强亚硝酸钠对 T2D 大鼠肝糖异生关键酶 mRNA 表达的抑制作用。亚硝酸钠和 NaSH 联合给药对糖异生的抑制作用与大鼠肝组织中 PI3K、Akt 和 eNOS 基因表达增加有关。
