Gooszen H G, van Schilfgaarde R, van der Burg M P, van Lawick van Pabst W P, Frölich M, Bosman F T
Department of Surgery, University Hospital Leiden, The Netherlands.
Transplantation. 1988 Dec;46(6):793-9. doi: 10.1097/00007890-198812000-00002.
In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.
在本研究中，我们定量评估了犬行胰管闭塞节段性胰腺自体移植后胰岛素分泌能力的变化。为此，我们采用了一种能同时测量流量的完整且未稀释的胰腺静脉血采样技术，通过该技术直接测定实际的胰岛素分泌能力。此外，还分析了组织学变化，以探讨胰岛素分泌能力变化的潜在机制。在胰管闭塞节段性胰腺自体移植前（I组，n = 8）、6周时（II组，n = 5）以及18 - 24个月时（III组，n = 7）测量左胰腺叶术中葡萄糖刺激的胰岛素分泌。在所有这3个时间点都进行了组织学分析。由于I - III组的实验是在全身麻醉下进行的，因此另外研究了第4组犬（IV组，n = 6），以确定全身麻醉对糖代谢的影响。K值似乎降至禁食清醒犬所得值的1/5，外周胰岛素反应（AUC）降至约1/3。尽管I - III组的所有动物在每个测试时间点的空腹血糖水平和K值均正常，但胰管闭塞移植后胰岛素分泌减少了75%。胰岛素分泌不仅显示出明显的定量变化，而且在葡萄糖刺激的胰岛素反应中发现了显著的定性改变。功能性胰岛结构紊乱似乎是胰岛素分泌减少的主要原因。如果应用于人类，我们的结果表明，特别是胰管闭塞的移植物，由于其内分泌能力有限，容易因最终排斥反应危机引起的损伤而丧失足够的移植物功能。
