Cyclosporine and islet mass--implications for islet transplantation.
Cyclosporine (CsA) is an inhibitor of ornithine decarboxylase (ODC), a key enzymatic step in cell proliferation. The purpose of this study was to determine the effect of CsA on islet cell mass. Partial obstruction (PDO) of the hamster pancreas is an established model of islet cell differentiation and proliferation in which regeneration is mediated by the induction of trophic activity (TA) that can be extracted from the pancreas. In Part 1 of these studies, hamsters were randomized to (i) Control (n = 5); (ii) PDO alone (n = 5); (iii) PDO + CsA (20 mg/kg ip daily) (n = 5); (iv) CsA alone (n = 5). On Day 21, 1 hr prior to sacrifice, animals received tritiated thymidine, 2 microCi/g body wt ip. Pancreata were excised for analysis of islet cell mass (No. islets/mm2) by morphometry and of cell proliferation (islet cell labeling index) by autoradiography. In Part 2 of these studies, hamsters were randomized to receive CsA (n = 34), as in Part 1, or saline (n = 30). After 7 days, animals received 1 ml of TA ip and were sacrificed after 0, 6, 8, and 10 hr. The pancreata were excised and determinations made of organ weight, DNA content, and ODC bioactivity (pmole/CO2/hr/mg DNA). Data (mean +/- SEM) were analyzed by ANOVA. In Part 1, the number of islets/mm2 in the PDO group was increased two-fold compared to control animals, those receiving CsA, and those undergoing PDO with CsA (2.4 +/- 0.1 vs 1.1 +/- 0.0, 1.4 +/- 0.2, 1.2 +/- 0.1, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Metrakos
P
P
Department of Surgery, Montreal General Hospital, McGill University, Canada.
Hornby
L
L
Rosenberg
L
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D016381:Islets of Langerhans Transplantation; D008647:Mesocricetus; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology
D016572:Cyclosporine; D009955:Ornithine Decarboxylase