Stöckmann F, Fehmann H C, Göke B, Siegel E G, Creutzfeldt W
Department of Medicine, University of Göttingen, FRG.
Transplantation. 1989 Sep;48(3):381-5. doi: 10.1097/00007890-198909000-00005.
Cyclosporine was fed to male Wistar rats in a dose of 5, 10, or 50 mg/kg b.wt. for 7 days, and the effect on insulin secretion from the isolated perfused pancreas was investigated. Dose-dependently plasma insulin and pancreatic insulin content decreased while whole-blood CsA levels increased. An increase in blood glucose was only observed after feeding 50 mg/kg b.wt. CsA resulting in whole-blood CsA levels of 7735 ng/ml. Glucose (20 mM)-stimulated total insulin secretion (ng/50 min) was not affected during feeding 5 mg/kg b.wt. CsA, but was significantly reduced after feeding 10 or 50 mg/kg b.wt. CsA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. during the initial peak (0-10 min) but not during the second peak (10-50 min), whereas after 10 or 50 mg/kg b.wt. CsA both peaks were markedly reduced. The arginine (20 mM) and the arginine (20 mM)-plus-glucose (20 mM) stimulated insulin secretion was less affected after feeding 10 mg/kg b.wt. CsA than after stimulation with glucose (20 mM) alone. The addition of CsA to the perfusate did not influence glucose-stimulated insulin release from normal rat pancreas. Our results demonstrate a toxic effect of CsA on the pancreatic beta cell that is dose dependent and possibly influences both insulin secretion and biosynthesis.
将环孢素以5、10或50mg/kg体重的剂量喂食雄性Wistar大鼠7天，并研究其对离体灌注胰腺胰岛素分泌的影响。血浆胰岛素和胰腺胰岛素含量呈剂量依赖性降低，而全血环孢素水平升高。仅在喂食50mg/kg体重的环孢素后观察到血糖升高，导致全血环孢素水平达到7735ng/ml。在喂食5mg/kg体重的环孢素期间，葡萄糖（20mM）刺激的总胰岛素分泌（ng/50分钟）不受影响，但在喂食10或50mg/kg体重的环孢素后显著降低。在初始峰值（0-10分钟）期间，5mg/kg体重的环孢素使双相胰岛素分泌减少，但在第二个峰值（10-50分钟）期间未减少，而在10或50mg/kg体重的环孢素后，两个峰值均明显降低。喂食10mg/kg体重的环孢素后，精氨酸（20mM）和精氨酸（20mM）加葡萄糖（20mM）刺激的胰岛素分泌比单独用葡萄糖（20mM）刺激后的影响小。向灌注液中添加环孢素不影响正常大鼠胰腺中葡萄糖刺激的胰岛素释放。我们的结果表明，环孢素对胰腺β细胞具有毒性作用，这种作用具有剂量依赖性，并且可能影响胰岛素分泌和生物合成。
