Synergistic effects of troglitazone and oleate on the translatability of preproinsulin mRNA from INS-1 cells

Glitazones are known to modulate fatty acid-induced effects on insulin secretion in the pancreatic beta-cell. The present study focused on combined effects of troglitazone and oleate on preproinsulin (PPI) biosynthesis. Insulin-producing INS-I cells were incubated for 4 hr at 11.2 mM glucose in the presence (O+) or absence (O-) of 200 muM oleate with (T+) or without (T-) 10 muM troglitazone. After cell lysis, cytoplasmic RNA was extracted and employed for Northern blotting and corresponding in vitro translation. Compared with untreated controls (CTRL = O-/T-), the cellular content of PPI-mRNA from cells which had been simultaneously treated by troglitazone and oleate (O+/T+) was significantly diminished (O+/T+ = 75 +/- 10% x CTRL; P = 0.015). The PPI-mRNA content from those cells which had been exclusively exposed either to oleate (O+/T-) or troglitazone (O-/T+) did not significantly differ from that of the untreated controls. In spite of that decreased PPI-mRNA content, in vitro translation revealed the highest yield of newly synthesized PPI in RNA samples from those cells which had been simultaneously exposed to oleate and troglitazone before (O+/T+ = 1.6 +/- 0.3 x CTRL; P = 0.01). It is concluded that troglitazone and oleate synergistically affect the translational rate at the level of the PPI-mRNA molecule. (C) 2002 Elsevier Science Inc. All rights reserved.