Delaunay C, Darquy S, Honiger J, Capron F, Rouault C, Reach G
INSERM Unité 341, Department of Diabetology, Hôtel-Dieu Hospital, Paris, France.
Artif Organs. 1998 Apr;22(4):291-9. doi: 10.1046/j.1525-1594.1998.05087.x.
The goal of this study was to determine whether porcine islets encapsulated in hollow fibers made of AN69 copolymer can correct hyperglycemia in diabetic mice and provide normal tolerance to a glucose challenge. In vitro perifusion of hollow fibers demonstrated the rapid kinetics of insulin release in response to glucose. Two fibers containing islets were transplanted into the peritoneal cavity of each of 17 streptozotocin induced diabetic mice. In 11 mice, diabetes was reversed within 3 days with plasma glucose levels decreasing from 19.7 +/- 0.9 (mean +/- SEM) before implantation to 10.9 +/- 0.8 mmol/L. Intraperitoneal glucose tolerance tests were performed in transplanted (n = 7), nondiabetic (n = 15), and diabetic mice (n = 6). A normal glucose pattern was observed in the transplanted diabetic mice. This was achieved in the presence of plasma insulin levels lower than those observed in control nondiabetic mice, suggesting the presence of a state of hypersensitivity to insulin, which was demonstrated in this model by exogenous insulin tolerance tests. In conclusion, encapsulation of islets suspended in ultraculture medium in biocompatible membranes of AN69 can provide xenograft survival, and complete normalization of glucose tolerance can be achieved.
本研究的目的是确定封装在由AN69共聚物制成的中空纤维中的猪胰岛是否能够纠正糖尿病小鼠的高血糖症，并使其对葡萄糖刺激具有正常的耐受性。中空纤维的体外灌流显示了胰岛素对葡萄糖反应的快速动力学。将两根含有胰岛的纤维移植到17只链脲佐菌素诱导的糖尿病小鼠的腹腔中。在11只小鼠中，糖尿病在3天内得到逆转，血浆葡萄糖水平从植入前的19.7±0.9（平均值±标准误）降至10.9±0.8 mmol/L。对移植小鼠（n = 7）、非糖尿病小鼠（n = 15）和糖尿病小鼠（n = 6）进行腹腔葡萄糖耐量试验。在移植的糖尿病小鼠中观察到正常的葡萄糖模式。这是在血浆胰岛素水平低于对照非糖尿病小鼠的情况下实现的，表明存在对胰岛素的超敏状态，这在该模型中通过外源性胰岛素耐量试验得到证实。总之，将悬浮在超培养基中的胰岛封装在AN69生物相容性膜中可以实现异种移植存活，并使葡萄糖耐量完全恢复正常。
