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Effect of experimental diabetes and insulin replacement on intestinal metabolism and excretion of 4-nitrophenol in rats

机译:实验性糖尿病和胰岛素替代对大鼠肠道代谢和4-硝基苯酚排泄的影响

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Luminal appearance of 4-nitrophenol (PNP) metabolites (4-nitrophenol-beta-glucuronide (PNP-G) and 4-nitrophenol-sulfate (PNP-S)) and activity of the related metabolic enzymes have been investigated in control and experimental diabetic rats. Experimental diabetes was induced by administration of streptozotocin (65 mg/kg i.v.). PNP (500 mu mol/L) was luminally perfused in the small intestine and the metabolites were determined in the perfusion solution. Effect of insulin replacement was also investigated in the diabetic rats. It was found that experimental diabetes increased the luminal appearance of PNP-G, which could be completely compensated by rapid-acting insulin administration (1 U/kg i.v.). Activities of the enzymes involved in PNP-G production (UDP-glucuronyltransferase and beta-glucuronidase) were also elevated; however, these changes were only partially compensated by insulin. Luminal appearance of PNP-S was not significantly changed by administration of streptozotocin and insulin. Activities of the enzymes of PNP-S production (sulfotransferases and arylsulfatases) did not change in the diabetic rats. The results indicate that experimental diabetes can provoke changes in intestinal drug metabolism. It increased intestinal glucuronidation of PNP but did not influence sulfate conjugation. No direct correlation was found between the changes of metabolic enzyme activities and the luminal appearance of the metabolites.
机译:在对照和实验糖尿病患者中,研究了4-硝基苯酚(PNP)代谢产物(4-硝基苯酚-β-葡糖醛酸苷(PNP-G)和4-硝基苯酚硫酸盐(PNP-S))的发光外观和相关代谢酶的活性。大鼠。通过施用链脲佐菌素(65mg / kg,静脉内)诱导实验性糖尿病。在小肠中对PNP(500μmol / L)进行光灌注,并在灌注溶液中测定代谢产物。还研究了糖尿病大鼠中胰岛素替代的作用。发现实验性糖尿病增加了PNP-G的管腔外观,这可以通过快速作用的胰岛素给药(1U / kg i.v.)完全补偿。与PNP-G产生有关的酶(UDP-葡萄糖醛酸转移酶和β-葡萄糖醛酸酶)的活性也增加了。然而,这些变化仅部分被胰岛素补偿。通过施用链脲佐菌素和胰岛素,PNP-S的发光外观没有明显改变。在糖尿病大鼠中,PNP-S产生酶(磺基转移酶和芳基硫酸酯酶)的活性未改变。结果表明,实验性糖尿病可以引起肠道药物代谢的改变。它增加了PNP的肠道葡萄糖醛酸苷化,但不影响硫酸盐结合。在代谢酶活性的变化与代谢产物的腔外观之间未发现直接相关性。

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