[Tumorigenesis after intra-portal pancreatic islet transplantation in diabetic rats].
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.
Dombrowski
F
F
Pathologisches Institut, Universität Bonn.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006801:Humans; D006946:Hyperinsulinism; D006965:Hyperplasia; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000379:methods* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D011169:Portal Vein; D011230:Precancerous Conditions / Q000473:pathology; D051381:Rats
Tumorentstehung nach intraportaler Pankreasinseltransplantation bei diabetischen Ratten.