Are Liver Cystic Lesions after Islet Transplantation Caused by Streptozotocine

Introduction: Pancreatic islets (PI) transplanted (Tx) into the portal vein cause a permanent exposure of surrounding liver tissue to insulin in high concentration. There were published several papers pronouncing the hypothesis of a direct triggering effect of Tx PI on a development of focal morphological changes in liver tissue (tumors, cysts). At the same time, streptozotocine (STZ) was supposed to play a minor but not negligible role in this phenomenon. Methods: Syngeneic pancreatic islets were transplanted into the healthy or diabetic (50mg/kg STZ) Brown Norway rats. Group A (n=5)-healthy, Tx of 450 PI into the portal vein; Group B (n=17)-STZ diabetes, Tx of 450 PI into the portal vein; Group C (n=8)-STZ diabetes, Tx of 100 PI under the left kidney capsule; Group D (n=7)-STZ diabetes, human insulin pellet s.c. (changed each 6 th week); All recipients were monitored for 10 months including MRI of liver. At the end of study each liver was examined by histology. The ultrastructure of liver was examined by electron microscopy (TEM) 3 hours after injection of STZ. Results: Tx of PI in suboptimal number normalized fasting blood glucose levels but did not normalize glucose assimilation during IVGTT in all diabetic animals. While liver of Group A recipients remained intact, in animals of Groups B and C multiple voluminous cystic complexes with cholangiocyte cubic epithelium lining were detected after 10 months irrespective of Tx site. In animals of Group D, blood glucose levels were nearly normalized six months after STZ injection and there was no need to replace pellets later on. There were simple, individual cystic lesions within liver in this group after 10 months. There were not any typical lesions in TEM examined samples. Conclusions: The injection of STZ and subsequent Tx of PI can cause cholagiogenic cystic lesions development in rats. The therapy by human insulin did not stimulate the development of cystic lesions by the equal efficiency. STZ itself cannot cause the cystic transformation of BN rat liver. Disclosure L. Kosinova: None. A. Patikova: None. E. Sticova: None. A. Vojtiskova: None. L. Bartonova: None. M. Cahova: None. J. Kriz: None.