Ar'Rajab A, Harris R B, Sentementes J T, Dawidson I J
Department of Surgery, University of Texas, Southwestern Medical Center at Dallas 75235-9031, USA.
Pancreas. 1996 Nov;13(4):372-80. doi: 10.1097/00006676-199611000-00006.
Studies of islet transplantation conducted immediately following diabetes induction may not accurately reflect the clinical situation. Long term preexisting diabetes with generalized microvasculature complication might adversely affect the outcome after islet transplantation. The present study testing this hypothesis by evaluating the effect of long-term preexisting diabetes on glucose-induced insulin secretion up to 6 months after transplantation of two different quantities of islets. One thousand two hundred or 2,400 islets were isotransplanted into the left renal subcapsular space at 10 days (acute diabetes), 3 months (chronic diabetes), or 6 months (long-term diabetes) after diabetes induction by streptozotocin in the rat. In addition, one group of diabetic rats in which normoglycemia was maintained with exogenous insulin treatment for 6 months was then transplanted with 1,200 islets. Intravenous glucose tolerance tests were performed at 10, 90, and 180 days after islet transplantation. Islet transplantation normalized the basal blood glucose levels within 24-48 h in all transplanted groups that remained normal for the entire study period of 6 months, with no differences among acute, chronic, or long-term diabetes. Basal plasma insulin levels were also normalized in all transplanted groups. Diabetic (acute, chronic, or long-term) rats transplanted with 2,400 islets achieved normal glucose-induced insulin secretion at 10 and 90 days after transplantation. In contrast, glucose-induced insulin secretion was impaired in rats transplanted with only 1,200 islets, with no differences among acute, chronic, and long term diabetes. However, at 180 days after transplantation, long term diabetic rats transplanted with 2,400 islets had impaired insulin secretion compared to normal controls. Insulin-treated long-term diabetic rats transplanted with 1,200 islets had normal glucose-induced insulin secretion at 10 days after transplantation. However, at 90 and 180 days after transplantation, insulin-treated long-term diabetic rats had impaired glucose-induced insulin secretion which was not different from nontreated transplanted long-term diabetic rats. It is concluded that long-term preexisting diabetes has no impact on the early outcome after islet transplantation. However, it may adversely affect the long-term function of the transplanted islets. Also, transplantation of a sufficient islet mass is the critical factor in achieving complete glucose homeostasis.
在糖尿病诱导后立即进行的胰岛移植研究可能无法准确反映临床情况。长期存在的糖尿病伴有全身性微血管并发症可能会对胰岛移植后的结果产生不利影响。本研究通过评估长期存在的糖尿病对移植两种不同数量胰岛后长达6个月的葡萄糖诱导胰岛素分泌的影响来验证这一假设。在大鼠经链脲佐菌素诱导糖尿病后的第10天（急性糖尿病）、3个月（慢性糖尿病）或6个月（长期糖尿病），将1200个或2400个胰岛同基因移植到左肾被膜下间隙。此外，一组用外源性胰岛素治疗维持血糖正常6个月的糖尿病大鼠随后移植1200个胰岛。在胰岛移植后第10、90和180天进行静脉葡萄糖耐量试验。在所有移植组中，胰岛移植在24 - 48小时内使基础血糖水平正常化，在整个6个月的研究期间保持正常，急性、慢性或长期糖尿病组之间无差异。所有移植组的基础血浆胰岛素水平也正常化。移植2400个胰岛的糖尿病（急性、慢性或长期）大鼠在移植后第10天和90天实现了正常的葡萄糖诱导胰岛素分泌。相比之下，仅移植1200个胰岛的大鼠葡萄糖诱导胰岛素分泌受损，急性、慢性和长期糖尿病组之间无差异。然而，在移植后180天，移植2400个胰岛的长期糖尿病大鼠与正常对照组相比胰岛素分泌受损。移植1200个胰岛的胰岛素治疗长期糖尿病大鼠在移植后第10天葡萄糖诱导胰岛素分泌正常。然而，在移植后90天和180天，胰岛素治疗长期糖尿病大鼠葡萄糖诱导胰岛素分泌受损，与未治疗的移植长期糖尿病大鼠无差异。结论是，长期存在的糖尿病对胰岛移植后的早期结果没有影响。然而，它可能会对移植胰岛的长期功能产生不利影响。此外，移植足够数量的胰岛是实现完全葡萄糖稳态的关键因素。
