摘要
目的 研究酶抑制剂对胰岛素在大肠和小肠吸收的影响 ,初步探讨酶抑制剂在肠道各段的作用机制。方法 采用原位肠袢法 ,设计肠道冲洗实验 ,测定胰岛素肠道吸收后的降血糖效应和血药浓度。结果 胰岛素单用于小肠袢或大肠袢时 ,冲洗实验前后均无降血糖效应。与酶抑制剂合用时 ,冲洗实验前 ,小肠段无降血糖效应 ,冲洗实验后 ,小肠段降血糖效应有所提高 ;冲洗实验前后 ,大肠段均产生明显的降血糖效应。酶抑制剂作用与其种类、应用浓度和不同区段内蛋白水解酶的活性有关 ;各种酶抑制剂提高胰岛素降血糖效应的顺序为 :亮肽素 >甘氨胆酸钠 >杆菌肽 >抑氨肽酶素B >胱蛋白 ;其中甘氨胆酸钠和杆菌肽还具有渗透促进作用。
Aim To study the effects of protease inhibitors on the large and small intestinal ab sorption of insulin in rats and to explore the mechanism of various protease inh ibitors in different intestinal regions. Methods The intestinal absorption of insulin was evaluated by its hypoglycemic effect an d serum insulin level using an in situ loop method with the washing treatmen t. Results Administration of insulin alone did not decrease the glucose level at either int estinal region with or without the washing treatment. With the unwashing treatme nt, there were no hypoglycemic effects in small intestinal loop when coadministr ation of insulin with protease inhibitors. With the washing treatment, the biolo gical effects of insulin were amplified a little in small intestinal loop; obvi ous hypoglycemic effects were found in large intestinal loop with or without th e washing treatment. The effectiveness of protease inhibitors was susceptible to their categories, concentrations and activities of proteolytic enzymes in diffe rent regions. The efficacy order of various protease inhibitors for enhancing hy poglycemic response of insulin was: leupeptin > sodium glycocholate > bacitracin > bestatin > cystatin; the percutaneous enhancement effects were observed in th e presence of either sodium glycocholate or bacitracin. Conclusion Coadministration of protease inhibitors could increase the insulin efficacy more effectively in the large intestine than in the small intestine.
出处
《药学学报》
CAS
CSCD
北大核心
2004年第2期140-143,共4页
Acta Pharmaceutica Sinica
基金
湖北省自然科学基金资助项目 ( 2 0 0 2AB1 1 5)
关键词
胰岛素
酶抑制剂
肠道吸收
降血糖效应
原位肠袢法
insulin
protease inhibitor
intestinal absorption
hypoglycemic effect
in si tu loop method
