Inhibitory effects of cyclosporin A on rat insulinoma cell proliferation, polyamine content and insulin secretion

Abstract

The effects of the immunosuppressive drug cyclosporin A on the growth and secretion of clonal rat insulinoma cells (RINm5F) was investigated in vitro. Particular attention was paid to the influence of cyclosporin A on the metabolism of polyamines, since these compounds have been implicated in regulation of the growth and function of insulin-producing cells. It was found that culture of the cells for 2 days in the presence of 0.1 mg/1 of cyclosporin A failed to affect RINm5F cell proliferation, polyamine content, cellular insulin content or secretion of insulin into the culture medium. When the concentration of cyclosporin A was raised to 1 mg/1, however, the growth rate and polyamine content of the cells were impeded in parallel with a decreased cellular insulin content and insulin secretion. Replenishment of the intracellular polyamine content by addition of exogenous putrescine failed to prevent the decreased growth rate and insulin content, indicating that cyclosporin A does not exert its inhibitory effect on the growth and insulin content of the RINm5F primarily by decreasing the polyamine content of these cells. Hence, cyclosporin A may be useful in decreasing the rapid growth of insulin-producing tumor cells, but also impairs insulin secretion.