Morsiani E, Rozga J, Dellagiacoma G, Demetriou A A
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Cell Transplant. 1997 Jan-Feb;6(1):17-22. doi: 10.1177/096368979700600105.
Poor engraftment and consequent loss of beta-cell mass could be one of the factors that are responsible for function loss after intraportal islet transplantation (Tx). Streptozotocin-diabetic rats were transplanted with syngeneic islets, which were injected into the portal vein via an indwelling catheter connected to a subcutaneous port. In Group I (n = 6), 1,000 islets were injected in a single dose into the liver. In Group II (n = 6), five doses of 200 islets were repeatedly injected over a period of 14 days, for a total of 1,000 islets. In Group III (n = 4), five decreasing doses of islets were injected over a period of 14 days, for a total of 750 islets. Nonfasting blood glucose (n-FBG) and body weight (b.wt.) were determined twice a week and an intravenous glucose tolerance test (IVGTT) was performed at 30 and 90 days. In Group I, n-FBG decreased in 2 wk from the time of first islet injection, averaging 110 +/- 21.9 mg/dl at 1 mo (p < 0.05 vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group II, n-FBG was normalized in 2 wk averaging 90.2 +/- 25 mg/dL on day 12 (p = NS vs. normal controls) and 75.8 +/- 14.6 mg/dL at 1 month (p = NS vs. normal controls); this value was maintained throughout the 3-mo duration of the study. In Group III, n-FBG decreased to normal values in 2 wk, averaging 77 +/- 15.7 mg/dL at 1 mo (p = NS vs. normal controls), but normoglycemia was maintained for 40 days and then followed by a progressive increase. Only in Group II, KG (percent/min decline in glucose level) was not significantly different from that of normal controls (1.702 +/- 0.531 at 1 mo and 1.676 +/- 0.891 at 3 mo), while it was significantly lower than normal controls in both Group I and III animals. Body weight increase after Tx correlated with the number of transplanted islets and at 90 days, Group III rats showed less increase than Groups I and II (p < 0.05), while no significant differences in b.wt. were recorded between Group I and II. The findings indicate that intraportal islet Tx, injected repeatedly and in small doses, produced better metabolic effects than injection of the same total number of islets in a single dose.
移植不佳以及随之而来的β细胞量损失可能是门静脉内胰岛移植（Tx）后功能丧失的原因之一。将链脲佐菌素诱导的糖尿病大鼠移植同基因胰岛，通过连接皮下端口的留置导管将胰岛注入门静脉。在第一组（n = 6）中，将1000个胰岛单次剂量注入肝脏。在第二组（n = 6）中，在14天内分五次重复注射200个胰岛，总共1000个胰岛。在第三组（n = 4）中，在14天内分五次递减剂量注射胰岛，总共750个胰岛。每周测定两次非空腹血糖（n-FBG）和体重（b.wt.），并在第30天和第90天进行静脉葡萄糖耐量试验（IVGTT）。在第一组中，自首次注射胰岛后2周n-FBG下降，1个月时平均为110±21.9mg/dl（与正常对照组相比，p<0.05）；在研究的3个月期间该值保持稳定。在第二组中，n-FBG在2周内恢复正常，第12天平均为90.2±25mg/dL（与正常对照组相比，p =无显著差异），1个月时为75.8±14.6mg/dL（与正常对照组相比，p =无显著差异）；在研究的3个月期间该值保持稳定。在第三组中，n-FBG在2周内降至正常水平，1个月时平均为77±15.7mg/dL（与正常对照组相比，p =无显著差异），但正常血糖维持40天，随后逐渐升高。仅在第二组中，KG（葡萄糖水平每分钟下降百分比）与正常对照组无显著差异（1个月时为1.702±0.531，3个月时为1.676±0.891），而在第一组和第三组动物中均显著低于正常对照组。Tx后体重增加与移植的胰岛数量相关，在90天时，第三组大鼠的体重增加低于第一组和第二组（p<0.05），而第一组和第二组之间的b.wt.无显著差异。研究结果表明，多次小剂量门静脉内注射胰岛比单次注射相同总数的胰岛产生更好的代谢效果。
