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.
Bollheimer
L Cornelius
LC
Department of Internal Medicine I, University of Regensburg, 93042, Regensburg, Germany. cornelius.bollheimer@klinik.uni-regensberg.de
Kagerbauer
Simone M
SM
Buettner
Roland
R
Kemptner
Daniela M
DM
Palitzsch
Klaus Dieter
KD
Schölmerich
Jürgen
J
Hügl
Sigrun R
SR
D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D004357:Drug Synergism; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D000078790:Insulin Secretion; D019301:Oleic Acid / Q000494:pharmacology*; D011384:Proinsulin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011498:Protein Precursors / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis; D000077288:Troglitazone
D002839:Chromans; D007328:Insulin; D011498:Protein Precursors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D019301:Oleic Acid; C013737:preproinsulin; D011384:Proinsulin; D000077288:Troglitazone