Sodium butyrate inhibits rat insulinoma cell proliferation without affecting the cellular insulin content or insulin release

Abstract

The short-chain carboxylic acid sodium butyrate is known to induce differentiation in several cell systems. In this paper we have investigated the effect of sodium butyrate on the growth rate and hormone content and secretion in clonal rat insulinoma cells (RINm5F). Special attention was paid to the role of polyamines for these processes, since these compounds have been implicated in the regulation of growth and function of insulin-producing cells. For this purpose RINm5F cells were maintained in culture for 4 days in the presence or absence of 1-2 mM sodium butyrate. It was found that sodium butyrate dose-dependently inhibited the proliferative activity of the RINm5F cells along with a decreased cellular polyamine content. The cellular content of insulin and secretion of the hormone into the culture medium were, however, not altered by sodium butyrate treatment, and neither did this treatment impose a glucose-sensitive insulin release. The decreased polyamine content was restored by the concomitant addition of exogenous putrescine; however, despite this, the reduced cell proliferation persisted. From these findings we conclude that the decreased growth rate evoked by sodium butyrate results from other events than specific polyamine synthesis inhibition. It is furthermore demonstrated that the processes of cell proliferation and regulation of cellular insulin content and secretion can be dissociated in the RINm5F cell line.