Hawthorne W J, Griffin A D, Lau H, Ekberg H, Allen R D
National Pancreas Transplant Unit, Westmead Hospital, New South Wales, Australia.
Transplantation. 1996 Aug 27;62(4):435-41. doi: 10.1097/00007890-199608270-00002.
In this canine study, glucose homeostasis after clinical pancreas transplantation is complex, with the relative effect of systemic versus portal delivery of insulin remaining unresolved. Thirty-two pancreatectomized dogs received either systemic venous drainage (SVD) with bladder exocrine drainage (n = 16), or portal venous drainage (PVD) with gastric exocrine drainage (n = 16). Cyclosporine (CsA) based immunosuppression was commenced on day -7. The effect of immunosuppression was a significant increase in fasting blood glucose (FBGL) (P = 0.002), fasting insulin (P = 0.024), AUC for insulin (P = 0.009), and K values decreased (P = 0.009). FBGL and K values remained abnormal after transplantation with no significant difference seen between SVD and PVD. However, fasting insulin became significantly lower after PVD and AUC insulin fell in both groups. CsA levels fell in both groups after transplantation, mirroring the fall in AUC insulin, and implicating CsA as a major cause of peripheral resistance to insulin. In conclusion, PVD did not demonstrate a significant advantage over SVD in handling an intravenous glucose challenge. The need for pancreatectomy in large animals may make them an unsatisfactory experimental model to evaluate the glucoregulatory effects of pancreas allotransplantation.
在这项犬类研究中,临床胰腺移植后的葡萄糖稳态较为复杂,胰岛素经体循环与经门静脉输送的相对作用仍未明确。32只接受胰腺切除的犬,其中16只接受体静脉引流(SVD)及膀胱外分泌引流,另外16只接受门静脉引流(PVD)及胃外分泌引流。在第-7天开始使用基于环孢素(CsA)的免疫抑制治疗。免疫抑制的作用是空腹血糖(FBGL)显著升高(P = 0.002)、空腹胰岛素显著升高(P = 0.024)、胰岛素曲线下面积(AUC)显著升高(P = 0.009),而K值降低(P = 0.009)。移植后FBGL和K值仍异常,SVD和PVD之间未见显著差异。然而,PVD后空腹胰岛素显著降低,两组的胰岛素AUC均下降。移植后两组的CsA水平均下降,与胰岛素AUC的下降情况相符,提示CsA是外周胰岛素抵抗的主要原因。总之,在应对静脉葡萄糖挑战方面,PVD并未显示出比SVD有显著优势。大型动物需要进行胰腺切除,这可能使其成为评估胰腺同种异体移植的糖调节作用的不理想实验模型。