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

Biochem Pharmacol. 2002 Dec 1;64(11):1629-36. doi: 10.1016/s0006-2952(02)01352-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromans / pharmacology*
  • Drug Synergism
  • Insulin / immunology
  • Insulin / metabolism
  • Insulin Secretion
  • Oleic Acid / pharmacology*
  • Proinsulin / drug effects
  • Proinsulin / genetics*
  • Proinsulin / metabolism
  • Protein Biosynthesis / drug effects*
  • Protein Precursors / drug effects
  • Protein Precursors / genetics*
  • RNA, Messenger / drug effects
  • Rats
  • Receptors, Cytoplasmic and Nuclear / biosynthesis
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / biosynthesis
  • Troglitazone

Substances

  • Chromans
  • Insulin
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Oleic Acid
  • preproinsulin
  • Proinsulin
  • Troglitazone