Lau T, Carlsson P-O, Leung P S
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Diabetologia. 2004 Feb;47(2):240-8. doi: 10.1007/s00125-003-1295-1. Epub 2004 Jan 13.
AIMS/HYPOTHESIS: A local angiotensin-generating system has been found in the exocrine pancreas. This study aimed, primarily, to investigate the existence of a local angiotensin-generating system in the pancreatic islets and, secondly, to elucidate its role in regulating insulin secretion.
Real-time RT-PCR and western blot were used to investigate if angiotensin-generating components are present in the mouse pancreatic islets, which are subject to regulation by islet transplantation. The localisation of AT1-receptors in islets was investigated by immunohistochemistry. Batch-type incubations of isolated islets were applied for studying the influence of angiotensin II on the glucose-stimulated insulin release, glucose oxidation and (pro)insulin, and total protein biosynthesis.
Major components, namely angiotensinogen, ACE, AT1- and AT2-receptors, were expressed in endogenous islets. AT1-receptors were localised to pancreatic beta cells. Exposure of the isolated islets to angiotensin II induced a dose-dependent inhibition of glucose-stimulated insulin release and inhibited (pro)insulin biosynthesis. This inhibitory action was fully preventable by pretreatment of the islets with losartan, an AT1-receptor antagonist. We also investigated if the expression of these components was changed after islet transplantation. Notably, a markedly increased expression of mRNA for the AT1-receptor was observed in islets retrieved from 4-week-old syngeneic islet transplants, a finding that was confirmed at the protein level.
CONCLUSION/INTERPRETATION: These data indicate the existence of an islet angiotensin-generating system of potential importance in the physiological regulation of glucose-induced insulin secretion, thus diabetes mellitus. The increased expression of the AT1-receptor in islet transplants could have relevance to islet-graft function.
目的/假设：已在外分泌胰腺中发现局部血管紧张素生成系统。本研究主要旨在调查胰岛中是否存在局部血管紧张素生成系统，其次是阐明其在调节胰岛素分泌中的作用。
采用实时逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法，研究血管紧张素生成成分是否存在于受胰岛移植调节的小鼠胰岛中。通过免疫组织化学研究胰岛中AT1受体的定位。应用分离胰岛的批量培养来研究血管紧张素II对葡萄糖刺激的胰岛素释放、葡萄糖氧化以及（前）胰岛素和总蛋白生物合成的影响。
主要成分，即血管紧张素原、血管紧张素转换酶（ACE）、AT1和AT2受体，在内源性胰岛中表达。AT1受体定位于胰腺β细胞。分离的胰岛暴露于血管紧张素II会导致葡萄糖刺激的胰岛素释放受到剂量依赖性抑制，并抑制（前）胰岛素生物合成。用AT1受体拮抗剂氯沙坦预处理胰岛可完全预防这种抑制作用。我们还研究了胰岛移植后这些成分的表达是否发生变化。值得注意的是，在4周龄同基因胰岛移植中回收的胰岛中观察到AT1受体的mRNA表达明显增加，这一发现在蛋白质水平得到证实。
结论/解读：这些数据表明存在一个胰岛血管紧张素生成系统，其在葡萄糖诱导的胰岛素分泌的生理调节中可能具有重要意义，从而对糖尿病也有重要意义。胰岛移植中AT1受体表达的增加可能与胰岛移植功能有关。
