硫氢化钠对 2 型糖尿病大鼠亚硝酸抑制的肾糖异生没有添加剂作用。
Sodium hydrosulfide has no additive effects on nitrite-inhibited renal gluconeogenesis in type 2 diabetic rats.
机构信息
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, Lund University, Malmö, Sweden.
出版信息
Life Sci. 2021 Oct 15;283:119870. doi: 10.1016/j.lfs.2021.119870. Epub 2021 Aug 2.
OBJECTIVE
Increased renal and hepatic gluconeogenesis are important sources of fasting hyperglycemia in type 2 diabetes (T2D). The inhibitory effect of co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on hepatic but not renal gluconeogenesis has been reported in rats with T2D. The present study aimed to determine the effects of co-administration of sodium nitrite and NaSH on the expression of genes involved in renal gluconeogenesis in rats with T2D.
METHODS
T2D was induced by a combination of a high-fat diet and low-dose streptozotocin (30 mg/kg). Male Wistar rats were divided into 5 groups (n = 6/group): Control, T2D, T2D + nitrite, T2D + NaSH, and T2D + nitrite+NaSH. Nitrite and NaSH were administered for nine weeks at a dose of 50 mg/L (in drinking water) and 0.28 mg/kg (daily intraperitoneal injection), respectively. Serum levels of urea and creatinine, and mRNA expressions of PEPCK, G6Pase, FBPase, PC, PI3K, AKT, PGC-1α, and FoxO1 in the renal tissue, were measured at the end of the study.
RESULTS
Nitrite decreased mRNA expression of PEPCK by 39%, G6Pase by 43%, FBPase by 41%, PC by 63%, PGC-1α by 45%, and FoxO1 by 27% in the renal tissue of rats with T2D; co-administration of nitrite and NaSH further decreases FoxO1, while had no additive effects on the tissue expression of the other genes. In addition, nitrite+NaSH decreased elevated serum urea levels by 58% and creatinine by 37% in rats with T2D.
CONCLUSION
The inhibitory effect of nitrite on gluconeogenesis in T2D rats is at least in part due to decreased mRNA expressions of renal gluconeogenic genes. Unlike effects on hepatic gluconeogenesis, co-administration of nitrite and NaSH has no additive effects on genes involved in renal gluconeogenesis in rats with T2D.
目的
在 2 型糖尿病（T2D）患者中，肾脏和肝脏的糖异生增加是空腹高血糖的重要来源。有报道称，在 T2D 大鼠中，亚硝酸钠和硫氢化钠（NaSH）联合给药可抑制肝脏但不抑制肾脏的糖异生。本研究旨在确定亚硝酸钠和 NaSH 联合给药对 T2D 大鼠肾脏糖异生相关基因表达的影响。
方法
采用高脂肪饮食联合小剂量链脲佐菌素（30mg/kg）诱导 T2D。雄性 Wistar 大鼠分为 5 组（每组 n=6）：对照组、T2D 组、T2D+亚硝酸钠组、T2D+NaSH 组和 T2D+亚硝酸钠+NaSH 组。亚硝酸钠和 NaSH 分别以 50mg/L（饮用水）和 0.28mg/kg（每日腹腔注射）的剂量给药 9 周。研究结束时，测量血清尿素和肌酐水平，以及肾脏组织中 PEPCK、G6Pase、FBPase、PC、PI3K、AKT、PGC-1α 和 FoxO1 的 mRNA 表达。
结果
亚硝酸钠使 T2D 大鼠肾脏组织中 PEPCK 的 mRNA 表达降低 39%，G6Pase 降低 43%，FBPase 降低 41%，PC 降低 63%，PGC-1α 降低 45%，FoxO1 降低 27%；亚硝酸钠和 NaSH 联合给药进一步降低了 FoxO1，但对其他基因的组织表达没有相加作用。此外，亚硝酸钠+NaSH 使 T2D 大鼠的血清尿素水平降低了 58%，肌酐水平降低了 37%。
结论
亚硝酸钠抑制 T2D 大鼠糖异生的作用至少部分归因于肾脏糖异生基因的 mRNA 表达降低。与对肝脏糖异生的作用不同，亚硝酸钠和 NaSH 联合给药对 T2D 大鼠肾脏糖异生相关基因没有相加作用。
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