Weitgasser R, Davalli A M, Capotorto J V, Finegood D T, Bonner-Weir S, Weir G C
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
Acta Med Austriaca. 1996;23(5):156-9.
Animal studies have been used to investigate different transplantation (Tx) sites to find best conditions for Tx in humans. A few long-term experiments of comparisons of different Tx-sites have been published. Therefore the aim of our study was to compare islet grafts transplanted under the kidney capsule (KTx) of male Lewis rats with grafts transplanted under the spleen capsule (STx) and to observe these animals over a period of 6 months. Diabetes was induced by Streptozotocin and rats were each transplanted with 2000 syngeneic islets under the kidney respectively the spleen capsule. 2 weeks after Tx all animals were normoglycemic. Over the following 6 months nearly normal plasma glucose levels could be maintained in the KTx group whereas the STx animals already became diabetic after 3 months. An oral glucose load after 2 months showed slightly elevated plasma glucose levels in the KTx group which only gained statistical significance in a similar test after 6 months. In the STx group definitely impaired glucose tolerance already prevailed at 2 months. An i.v. glucose tolerance test performed 6 months after Tx showed a loss of first phase insulin release in both Tx groups but an increased second phase release and a preserved response to L-arginine compared to controls. Insulin content remained unchanged in the KTx group, but was markedly reduced in the STx group after 6 months. In conclusion we may say that KTx is able to establish near-normoglycemia in streptozotocin-diabetic Lewis rats which can be maintained over a long period of time despite abnormal glucose tolerance and impaired insulin secretion STx could normalize plasma glucose only up to 3 months showing early impairment of glucose and insulin regulation. If KTx has immunological or local advantages (islet vascularization, innervation) compared to STx with higher dispersion of islets in spleen and portal vascular system remains unclear.
动物研究已被用于调查不同的移植部位，以寻找人类移植的最佳条件。已发表了一些关于不同移植部位比较的长期实验。因此，我们研究的目的是比较雄性Lewis大鼠肾被膜下移植的胰岛移植物（KTx）与脾被膜下移植的移植物（STx），并对这些动物进行6个月的观察。通过链脲佐菌素诱导糖尿病，分别将2000个同基因胰岛移植到大鼠的肾被膜下和脾被膜下。移植后2周，所有动物血糖正常。在接下来的6个月里，KTx组的血浆葡萄糖水平几乎可以维持在正常水平，而STx组的动物在3个月后就已经出现糖尿病。2个月后的口服葡萄糖耐量试验显示，KTx组的血浆葡萄糖水平略有升高，仅在6个月后的类似试验中具有统计学意义。在STx组，2个月时就已经出现明显的葡萄糖耐量受损。移植后6个月进行的静脉葡萄糖耐量试验显示，两个移植组均出现第一相胰岛素释放丧失，但与对照组相比，第二相释放增加，对L-精氨酸的反应保留。KTx组的胰岛素含量保持不变，但STx组在6个月后明显降低。总之，我们可以说，KTx能够在链脲佐菌素诱导糖尿病的Lewis大鼠中建立接近正常的血糖水平，尽管葡萄糖耐量异常和胰岛素分泌受损，但仍能长期维持。STx只能使血浆葡萄糖在3个月内恢复正常，显示出早期的葡萄糖和胰岛素调节受损。与STx相比，KTx是否具有免疫学或局部优势（胰岛血管化、神经支配），以及胰岛在脾脏和门静脉系统中分布更分散，目前尚不清楚。
