ADVERSE-EFFECTS OF CYCLOSPORINE ON ISLET GROWTH AND DIFFERENTIATION

In light of recent evidence that cyclosporine (CsA) inhibits growth of the exocrine pancreas, we decided to examine the effects of cyclosporine in a hamster model of islet cell proliferation and differentiation induced by partial pancreatic duct obstruction (PPDO), in which the growth of pancreatic endocrine tissue is mediated by production of an islet cell growth factor (ICGF) contained in a cytosolic extract of pancreas. In Part I of this study, extract was prepared from PPDO pancreas, from PPDO pancreas in animals treated with CsA (20 mg/kg ip daily for 10 days), and from pancreas in control animals. Data obtained from an in vivo bioassay confirmed that administration of the extract derived from PPDO and PPDO + CsA animals increased pancreatic organ weight significantly by 10 and 17%, respectively, compared to control. Similarly, total pancreatic DNA content was increased significantly by 25 and 41%, respectively. In Part II of the study, the direct effect of CsA on islet cell proliferation and differentiation induced by PPDO was examined. The number of islets per square millimeter and the uptake of tritiated thymidine by islet cells (%) were increased significantly in PPDO animals (2.4 ± 0.1 and 0.56 ± 0.06) compared to those in PPDO + CsA animals (1.2 ± 0.1 and 0.24 ± 0.01) and to those in controls (1.1 ± 0.0 and 0.22 ± 0.07). It is concluded from the data in Part I that CsA does not inhibit ICGF production, but the results of Part II suggest that CsA acts to block ICGF activity. If the capacity for continued islet cell proliferation in islet allografts in the post-transplant period is important, our findings may have implications for successful islet transplantation in man. © 1990.