糖适平诱导离体大鼠胰岛β细胞脱敏及敏感性恢复的研究  

Gliquidon Induced-desensitization of Pancreatic β Cells and the Partial Reversion of Responsiveness after the Desensitization of Exposure to Drug in Normal and STZ Type 2 Diabetic Rats

作　　者：王双[1] 李秀钧[2] 羊海燕[3] 赵桂芝[2] 

机构地区：[1]四川大学华西医院老年病科,成都610041 [2]四川大学华西医院内分泌科 [3]四川省建筑医院内科

出　　处：《四川大学学报（医学版）》2004年第3期398-401,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的　探讨糖适平诱导离体大鼠胰岛 β细胞脱敏及敏感性恢复的规律。方法　采用小剂量链脲佐菌素(STZ2 5 mg/ kg)腹腔一次注射并高热量饮食的方法建立肥胖 2型糖尿病模型 ,观察不同剂量的糖适平 (5 0 0、10 0 0、15 0 0 ng/ m l)在不同作用时间对正常和 2型糖尿病鼠离体胰岛细胞胰岛素分泌的影响 ,了解糖适平对胰岛 β细胞脱敏及敏感性恢复的条件。结果　 5 0 0、10 0 0 ng/ ml的糖适平刺激正常鼠胰岛 β细胞能于 2 h时产生胰岛素分泌高峰 ,以后逐渐下降 ,而 15 0 0 ng/ ml糖适平则无此现象 ;不同剂量糖适平预处理的正常鼠胰岛 β细胞对相应剂量糖适平的即刻刺激均无反应 ,10 m in短期脱敏不能使胰岛素分泌恢复 ,2 0 h长期脱敏 ,胰岛素分泌在 5 0 0 ng/ m l糖适平刺激时能完全恢复。结论　鼠胰岛 β细胞对糖适平诱导的脱敏作用及敏感性恢复具有时间和剂量依赖性。Objective To test if gliquidone (gli) induces β cells desensitization as other sulfonylurea (Su) and the features of the reversion of responsiveness. Methods An obese type 2 diabetic (DM2) rat model was developed, for which low dose streptozocin (STZ,25 mg/L) was injected ip. into Wistar rats followed by high sucrose-fat diet feeding for 8 weeks as described previously. Islet cells from normal and DM2 rats were isolated and cultured over 24 h in a medium with or without gli and the static Ins secretion at various time intervals were measured by RIA. These islet cells either untreated or pre-treated for 24 h with various dosages of gli (500;1000;1500 ng/ml) were perifused by a column perifusion system. Ins release in response to the corresponding doses of gli was evaluated. Results Insulin secretion decreased remarkably under the static stimuli to DM2 islets, compared with that of the normal controls (P<0.05). Insulin secretion in normal islets in response to 500 and 1000 ng/ml gli rose to a peak level at the second hour, and then declined with the time, but the islets did not respond to 1500 ng/ml gli. Gli pre-treated islets gave no response to acute gli stimuli. Short term (10 min) removal of the islets from gli-exposure could not reverse the responsiveness; however, after the exposure to gli being discontinued for 20 h, desensitization could be reverted completely in use of 500 ng/ml gli; partially in use of 1000 ng/ml gli; but not in use of 1500 ng/ml gli. Conclusion The results indicated that the exposure of β cell to gli at various concentrations induced selective desensitization of the β cell to gli stimuli; and the desensitization could be reverted completely or partially after the exposure being discontinued for 20 h to 500 ng/ml and 1000 ng/ml but not to 1500 ng/ml gli, respectively. The restoration of the response of β cell to gli stimuli was dose-dependent and time-dependent.

关 键 词：胰岛Β细胞 格列喹酮(糖适平) 脱敏 胰岛素分泌 

分 类 号：R96[医药卫生—药理学]