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-1 cells were incubated for 4 hr at 11.2mM glucose in the presence (O(+)) or absence (O(-)) of 200 microM oleate with (T(+)) or without (T(-)) 10 microM 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.