Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts
Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts
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DOI：
10.1007/s00125-005-1761-z
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发表时间：
2005-06-01
期刊：
影响因子：
8.2
通讯作者：
Carlsson, PO
中科院分区：
文献类型：
--
作者：
Kampf, C;Lau, T;Carlsson, PO
目的/假设：我们最近发现的证据，血管紧张素生成系统在胰岛。本研究探讨了内源性血管紧张素II对移植胰岛微循环和功能的影响。材料与方法：氯沙坦，一种血管紧张素II 1型受体抑制剂，急性静脉注射给4周龄胰岛肾包膜下移植的小鼠，或在最后14天或整个移植后4周期间添加到饮用水中。在某些情况下，将移植肾解剖并在体外灌注，以评估血管紧张素II和氯沙坦对葡萄糖刺激的移植物胰岛素释放的影响。结果如下：在移植后4周期间，氯沙坦治疗对胰岛血管重建以及胰岛移植物胰岛素释放有负面影响。然而，在形成新的血管网络后，静脉或口服氯沙坦可改善胰岛移植物的血液灌注。氯沙坦也能有效改善胰岛移植物中的P-O2。移植物灌注实验表明，当暴露于氯沙坦时，移植胰岛中葡萄糖刺激的胰岛素释放的第一相明显更好。相反，急性血管紧张素II的管理减少胰岛移植物血流量，PO 2和葡萄糖刺激的胰岛素释放。结论/解释：本研究表明，抑制胰岛肾素-血管紧张素系统可能是一种可行的策略，以增加血液灌注，PO 2和胰岛移植物的功能。然而，在胰岛血管系统形成之前，不应开始这种治疗。
Aims/hypothesis: We recently found evidence of an angiotensin-generating system in pancreatic islets. The present study investigated the effect of endogenously produced angiotensin II on microcirculation and function in transplanted islets. Materials and methods: Losartan, an angiotensin II type 1 receptor inhibitor, was administered either acute intravenously to mice with 4-week-old islet renal subcapsular transplants, or added to the drinking water for the final 14 days or throughout the 4-week post-transplantation period. The graft-bearing kidney was, in some cases, dissected out and perfused in vitro to evaluate the effect of angiotensin II and losartan on glucose-stimulated insulin release from the grafts. Results: Losartan treatment throughout the 4-week post-transplantation period had negative effects on islet revascularisation as well as on islet graft insulin release. However, administration of losartan, either intravenously or orally, after the formation of a new vascular network, improved islet graft blood perfusion. P-O2 in the islet transplants was also effectively improved by the losartan treatment. Graft perfusion experiments showed a markedly better first phase of glucose-stimulated insulin release in transplanted islets when exposed to losartan. In contrast, acute administration of angiotensin II decreased islet graft blood flow, PO2 and glucose-stimulated insulin release. Conclusions/interpretations: This study shows that inhibition of the islet reninangiotensin system may be a feasible strategy to increase the blood perfusion, PO2 and function within islet grafts. Such treatment should not be initiated, however, before the islet vascular system has been formed.