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 β-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 11.2 mM glucose in the presence (O+) or absence (O−) of 200 μM oleate with (T+) or without (T−) 10 μM troglitazone. After cell lysis, cytoplasmic RNA was extracted and employed for Northern blotting and corresponding in vitro translation. Compared with untreated controls (<F>CTRL=O−/T−</F>), the cellular content of PPI-mRNA from cells which had been simultaneously treated by troglitazone and oleate (O+/T+) was significantly diminished (<F>O+/T+=75±10%×CTRL</F>; <F>P=0.015</F>). 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 (<F>O+/T+=1.6±0.3×CTRL</F>; <F>P=0.01</F>). It is concluded that troglitazone and oleate synergistically affect the translational rate at the level of the PPI-mRNA molecule. [Copyright &y& Elsevier]