THE EVOLUTION OF FUNCTION AND RESPONSE TO ARGININE CHALLENGE AND PREGNANCY OF PORTALLY AND SYSTEMICALLY PLACED ISLET CELL GRAFTS IN STREPTOZOTOCIN DIABETIC MICE

THE EVOLUTION OF FUNCTION AND RESPONSE TO ARGININE CHALLENGE AND PREGNANCY OF PORTALLY AND SYSTEMICALLY PLACED ISLET CELL GRAFTS IN STREPTOZOTOCIN DIABETIC MICE
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DOI:
10.1016/0026-0495(90)90179-g
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发表时间:
1990-12-01
影响因子:
9.8
通讯作者:
MANDEL, TE
MANDEL, TE
中科院分区:
医学1区
文献类型:
--
作者:
GILLIES, MC;MANDEL, TE

文献摘要

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用链脲佐菌素致糖尿病的小鼠在门静脉(PG)或全身血管床(SG)接受器官培养的胎儿胰岛细胞移植物,以确定胰岛素的门静脉输送是否是移植物放置的重要考虑因素。根据体重和血糖的测定,SG小鼠的移植物建立得更快。在注射后5分钟测量血清胰岛素时使用的剂量,发现腹腔精氨酸比静脉葡萄糖具有更强的胰岛素促分泌剂。两组小鼠对精氨酸刺激的葡萄糖反应最初都不正常,但在移植后4个月与正常对照相同,表明移植是一个渐进的过程。然后对小鼠进行交配,观察它们对妊娠期慢性血糖应激的反应。与未经治疗的糖尿病患者相比,PG和SG小鼠的生育率正常,没有一只怀孕。与历史对照组相比,子代产仔数、体重、畸形率和胰腺胰岛素含量均正常。除了妊娠第19.5天糖化血红蛋白水平升高(5.5%和5.5% v 3.7%, P < 0.01)外,PG组和SG组母亲在妊娠期间表现正常。因此,我们无法发现门静脉置放和系统置放胰岛移植物之间的任何区别。
Mice made diabetic with streptozotocin received organ cultured fetal islet cell grafts in the portal (PG) or systemic (SG) vascular beds in order to determine whether portal delivery of insulin is an improtant consideration in graft placement. Grafts were established more quickly in SG mice as shown by body weight and blood glucose estimations. Intraperitoneal arginine was found to be a stronger insulin secretagogue than intravenous glucose with the doses used when serum insulin was measured 5 minutes after injection. Glucose response to an arginine challenge was initially abnormal in both groups of mice, but was identical to normal controls 4 months after transplantation, showing that engraftment is a gradual process. Mice were then mated and their response to the chronic glycemic stress of pregnancy was noted. PG and SG mice had normal fertility rates in contrast to untreated diabetics, none of which became pregnant. Offspring were normal with respect to litter size, body weight, malformation rate, and pancreatic insulin content compared with historical controls. PG and SG mothers behaved normally during pregnancy, with the exception of a raised glycoslyated hemoglobin level at day 19.5 gestation (5.5% and 5.5% v 3.7%, P < .01). We were, therefore, unable to detect any difference between portally and systemically placed islet grafts.