Scharp D W, Marchetti P, Swanson C, Newton M, McCullough C S, Olack B
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
Cell Transplant. 1992;1(2-3):245-54. doi: 10.1177/0963689792001002-306.
Determination of the long-term function of islet transplantation in relation to the implantation site and the numbers of islets is of scientific interest and, with human islet transplant trials in progress, is a pressing clinical question. In this study, highly purified canine islets were isolated by collagenase digestion and Ficoll purification, and autotransplanted into either the spleen (in 10 dogs) or the liver (in 12 dogs). Dogs transplanted with islets into the spleen or liver received 264,300 +/- 20,300 (mean +/- SEM) and 158,600 +/- 15,000 islet equivalents (150-microns-sized islets) respectively. Graft survival at 1 yr was 86% in intrasplenic islet autografts (ISTx) and 50% in intraportal islet autografts (IPTx). Intravenous glucose tolerance tests and mixed meal-oral glucose tests were performed 1-12 mo from islet transplantation. Compared to controls, ISTx and IPTx dogs showed a similar decrease of glucose tolerance after both intravenous glucose tolerance tests and mixed meal-oral glucose tests. On intravenous glucose tolerance tests, plasma insulin levels were lower in ISTx than in IPTx dogs and controls. On mixed meal-oral glucose tests, insulin values were higher in IPTx dogs than in controls. There was a positive correlation (r = .56, p < 0.05) between the number of transplanted islet equivalents and the K values. These results demonstrate that, in dogs with islet transplant: 1) long-term islet survival can be achieved in the spleen better than in the liver; 2) islet survival is related to the mass of transplanted islets in the spleen, but not in the liver, where other factors probably affect islet survival; 3) the ability of metabolizing glucose is reduced after both intrasplenic and intraportal islet autografts; 4) both reduced insulin secretion (predominant in ISTx dogs on intravenous glucose tolerance testing) and insulin resistance (predominant in IPTx dogs on mixed meal-oral glucose tests) are the probable causes of the decreased glucose tolerance.
确定胰岛移植的长期功能与植入部位及胰岛数量之间的关系具有科学意义，并且随着人类胰岛移植试验的进行，这也是一个紧迫的临床问题。在本研究中，通过胶原酶消化和Ficoll纯化分离出高度纯化的犬胰岛，并将其自体移植到脾脏（10只犬）或肝脏（12只犬）中。移植胰岛至脾脏或肝脏的犬分别接受了264,300±20,300（平均值±标准误）和158,600±15,000个胰岛当量（150微米大小的胰岛）。脾内胰岛自体移植（ISTx）1年时的移植物存活率为86%，门静脉内胰岛自体移植（IPTx）为50%。在胰岛移植后1至12个月进行静脉葡萄糖耐量试验和混合餐-口服葡萄糖试验。与对照组相比，ISTx和IPTx犬在静脉葡萄糖耐量试验和混合餐-口服葡萄糖试验后葡萄糖耐量均有类似程度的降低。在静脉葡萄糖耐量试验中，ISTx犬的血浆胰岛素水平低于IPTx犬和对照组。在混合餐-口服葡萄糖试验中，IPTx犬的胰岛素值高于对照组。移植的胰岛当量数量与K值之间存在正相关（r = 0.56，p < 0.05）。这些结果表明，在进行胰岛移植的犬中：1）胰岛在脾脏中的长期存活比在肝脏中更好；2）胰岛存活与脾脏中移植胰岛的数量有关，但与肝脏中移植胰岛的数量无关，在肝脏中可能有其他因素影响胰岛存活；3）脾内和门静脉内胰岛自体移植后代谢葡萄糖的能力均降低；4）胰岛素分泌减少（在静脉葡萄糖耐量试验中以ISTx犬为主）和胰岛素抵抗（在混合餐-口服葡萄糖试验中以IPTx犬为主）均可能是葡萄糖耐量降低的原因。
