Evert Matthias, Schneider-Stock Regine, Dombrowski Frank
Department of Pathology, Otto-von-Guericke-University, Magdeburg, Germany.
Pathol Res Pract. 2003;199(6):373-9. doi: 10.1078/0344-0338-00433.
After low-number transplantation of islets of Langerhans into the liver of streptozotocin-diabetic rats, the hepatocytes in the acini, draining the blood from the islets, are exposed to a local hyperinsulinemia, whereas the remaining tissue is affected by hypoinsulinemia. In this model, insulin induces alterations that resemble preneoplastic foci of altered hepatocytes (FAH) and develop into hepatocellular tumors in later stages of carcinogenesis. In rodents, apolipoprotein A-IV (A-IV) is synthesized in the small intestine and the liver. Whereas intestinal production is mainly influenced by lipid intake and chylomicrone formation, little is known about mechanisms regulating hepatic A-IV synthesis. As it is known that insulin modulates lipoprotein metabolism in different ways, we investigated the effect of insulin on hepatocytic A-IV mRNA expression in this model. After Laser microdissection of FAH and quantitative RT-PCR (LightCycler), we found a 3.2 to 7.4-fold increase of A-IV mRNA in the FAH. To the best of our knowledge, these results represent the first data of insulin-stimulated A-IV mRNA overexpression in rat hepatocytes in vivo, and are in line with previously reported results of experiments with cultured hepatocytes. It remains to be elucidated whether A-IV mRNA overexpression is only an epiphenomenon of insulin action or is relevant for hepatocarcinogenesis in this model.
将少量胰岛移植到链脲佐菌素诱导的糖尿病大鼠肝脏后，胰岛引流血液的腺泡中的肝细胞会暴露于局部高胰岛素血症，而其余组织则受低胰岛素血症影响。在这个模型中，胰岛素诱导的改变类似于肝细胞改变的癌前病灶（FAH），并在致癌作用的后期发展为肝细胞肿瘤。在啮齿动物中，载脂蛋白A-IV（A-IV）在小肠和肝脏中合成。虽然肠道产生主要受脂质摄入和乳糜微粒形成的影响，但关于调节肝脏A-IV合成的机制知之甚少。由于已知胰岛素以不同方式调节脂蛋白代谢，我们在这个模型中研究了胰岛素对肝细胞A-IV mRNA表达的影响。通过对FAH进行激光显微切割和定量RT-PCR（LightCycler），我们发现FAH中A-IV mRNA增加了3.2至7.4倍。据我们所知，这些结果代表了体内大鼠肝细胞中胰岛素刺激的A-IV mRNA过表达的首批数据，并且与先前报道的培养肝细胞实验结果一致。A-IV mRNA过表达是否仅仅是胰岛素作用的一种附带现象，或者在这个模型中与肝癌发生是否相关，仍有待阐明。
