Reversal of streptozotocin-incluced hyperglycemia by transplantation of pseudoislets consisting of β cells derived from ductal cells
Reversal of streptozotocin-incluced hyperglycemia by transplantation of pseudoislets consisting of β cells derived from ductal cells
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DOI：
10.1507/endocrj.51.381
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发表时间：
2004-06-01
影响因子：
2
通讯作者：
Kojima, I
中科院分区：
文献类型：
--
作者：
Ogata, T;Park, KY;Kojima, I
本研究试图通过移植来源于胰腺导管细胞的β细胞来治疗链脲佐菌素(STZ)诱导的高血糖。取新生大鼠乳腺导管细胞进行体外培养。经β细胞蛋白和激活素A孵育后，约70%的细胞转化为胰岛素分泌细胞。分化细胞对去极化浓度的钾、甲苯丁胺和高浓度葡萄糖有反应，胰岛素分泌分别增加2.5、2.3和1.6个单位。然后，我们用分化后的细胞制备了假性胰岛，它表现出极大的葡萄糖反应性，高浓度的葡萄糖诱导胰岛素分泌增加3倍。我们将这些假性胰岛移植到STZ处理的裸鼠的门静脉内。移植前血糖浓度在400 mg/dl以上，移植后血糖明显下降，并持续两周。这些结果表明，STZ诱导的高血糖可以通过移植由导管细胞来源的0细胞组成的伪胰岛来治疗。
The present study was conducted in an attempt to treat streptozotocin (STZ)-induced hyperglycemia by transplanting beta cells derived from pancreatic ductal cells. Ductal cells obtained from neonatal rats were cultured in vitro. Approximately 70% of the cells were converted to insulin-secreting cells by incubating with betacellulin and activin A. Differentiated cells responded to a depolarizing concentration of potassium, tolbutamide and a high concentration of glucose, and insulin secretion increased by 2.5-, 2.3- and 1.6-fotd, respectively. We then prepared pseudoislets using the differentiated cells, which exhibited greatly improved glucose-responsiveness, with a high concentration of glucose inducing a 3-fold increase in insulin secretion. We transplanted these pseudoislets into the portal vein of STZ-treated nude mice. Before transplantation, the plasma glucose concentration was above 400 mg/dl, and after transplantation it was markedly reduced, the effect of which persisted for two weeks. These results indicate that STZ-induced hyperglycemia can be treated by transplanting pseudoislets consisting of 0 cells derived from ductal cells.