Dombrowski F
Pathologisches Institut, Universität Bonn.
Verh Dtsch Ges Pathol. 2000;84:136-50.
In a novel model of hepatocarcinogenesis, a low number of isologous pancreatic islets were transplanted via the portal veins into the livers of streptozotocin-diabetic rats. The number of islets is chosen so low, that the diabetic state is only ameliorated by the islet transplantation. The permanent high blood glucose stimulates the beta-cells of the islet transplants to permanent maximal synthesis and secretion of insulin which causes hyper-insulinemia in the liver acini downstream of the transplants. The hepatocytes of these acini show alterations which are typical for insulin effects but also for glycogen storing foci of altered hepatocytes induced by different protocols of experimental hepatocarcinogenesis in different species, and which are also found in human preneoplastic liver foci. Indeed, the altered hepatocytes after low-number islet transplantation proceeded in long-term experiments to hepatocellular adenomas and hepatocellular carcinomas. Hyperplasia of islet cells developed in the transplanted islets, as a consequence of hyperglycemia which for the beta cells is not only a secretory, but also a proliferative stimulus. Six out of 33 animals between the 18th and the 24th month after islet transplantation changed from hyperglycemia to severe hypoglycemia, due to insulinomas which had developed in the liver from the transplanted islets. Development of hepatocellular tumors as well as insulinomas start in this model with alterations, which have been shown to be of preneoplastic nature. They can be understood as local pathological adaptative phenomena without the postulate of a primary genetic damage.
在一种新型肝癌发生模型中，将少量同源胰岛经门静脉移植到链脲佐菌素诱导的糖尿病大鼠肝脏中。所选择的胰岛数量极少，以至于胰岛移植仅能改善糖尿病状态。持续的高血糖刺激移植胰岛的β细胞持续进行最大量的胰岛素合成与分泌，这在移植下游的肝腺泡中导致高胰岛素血症。这些腺泡的肝细胞出现的改变，既是胰岛素作用的典型表现，也是不同物种通过不同实验性肝癌发生方案诱导的肝细胞糖原储存灶改变的典型表现，并且在人类癌前肝病灶中也能发现。实际上，在长期实验中，少量胰岛移植后的肝细胞改变发展为肝细胞腺瘤和肝细胞癌。由于高血糖对β细胞而言不仅是一种分泌刺激，也是一种增殖刺激，移植胰岛中出现了胰岛细胞增生。胰岛移植后第18至24个月期间，33只动物中有6只因移植胰岛在肝脏中形成胰岛素瘤而从高血糖转变为严重低血糖。在这个模型中，肝细胞肿瘤以及胰岛素瘤的发生始于已被证明具有癌前性质的改变。它们可被理解为局部病理适应性现象，无需假定存在原发性基因损伤。
