Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China.
Sci Rep. 2013;3:1377. doi: 10.1038/srep01377.
We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled (13)C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na(+)/K(+)-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes.
我们研究了 1-脱氧野尻霉素（DNJ）在正常和糖尿病小鼠的葡萄糖吸收和代谢中的作用。口服和静脉葡萄糖耐量试验以及标记（13）C6-葡萄糖摄取试验表明，DNJ 抑制了肠道中的葡萄糖吸收。我们还表明，DNJ 下调了肠道 SGLT1、Na(+)/K(+)-ATP 和 GLUT2 mRNA 和蛋白表达。DNJ（50mg/kg）预处理增加了肝糖酵解酶（GK、PFK、PK、PDE1）的活性、mRNA 和蛋白水平，并降低了糖异生酶（PEPCK、G-6-Pase）的表达。肝细胞蛋白表达测定和纯化酶的体外试验表明，葡萄糖糖酵解酶活性的增加是由于蛋白表达的相对增加，而不是直接的酶激活。这些结果表明，DNJ 通过直接调节参与葡萄糖转运系统、糖酵解和糖异生酶的蛋白表达来抑制肠道葡萄糖吸收并加速肝脏葡萄糖代谢。
