Sensitivity to pentamidine but resistance to streptozotocin of tumoral insulin-producing cells (RINm5F line).
Pancreatic islets removed from normal rats and tumoral insulin-producing cells of the RINm5F line were examined for their respective sensitivity to two distinct beta-cytotoxic agents, namely pentamidine and streptozotocin. After 20 h of culture in the presence of pentamidine (5-500 microM), a dose-related decrease in both insulin output and D-[5-3H] glucose utilization was observed in pancreatic islets. Under identical conditions, pentamidine caused a dose-related destruction of RINm5F cells and, in the remaining cells, also impaired D-[5-3H] glucose utilization. When pancreatic islets were exposed for 60 or 120 min to streptozotocin (3.77 mM), both the utilization of D-[5-3H] glucose and oxidation of D-[U-14C] glucose were impaired. However, under identical conditions, the RINm5F cells appeared resistant to the cytotoxic action of streptozotocin. Since streptozotocin, but not pentamidine, is thought to be transported into islet cells at the intervention of a hexose carrier, these findings support the concept that a low efficiency of this carrier-mediated process represents a fundamental defect of the RINm5F cells.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects*; D010419:Pentamidine / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology*; D013997:Time Factors
D000578:Amidines; D007328:Insulin; D013311:Streptozocin; D010419:Pentamidine