Vanadium compounds modulate PPAR gamma activity primarily by increasing PPAR gamma protein levels in mouse insulinoma NIT-1 cells

Vanadium compounds are promising agents in the therapeutic treatment of diabetes; however, their mechanism of action has not been clearly elucidated. The current study investigated the effects of vanadium compounds, vanadyl acetylacetonate [(VO)-O-IV(acac)(2)] and sodium metavanadate ((NaVO3)-O-V), on peroxisome proliferator-activated receptors (PPARs), especially PPAR gamma, which are important targets of anti- diabetic drugs. Our experimental results revealed that treatment of NIT-1 beta-pancreas cells with vanadium compounds resulted in PPAR gamma activation and elevation of PPAR gamma protein levels. Vanadium compounds did not increase PPAR gamma transcription but ameliorated PPAR gamma degradation induced by inflammatory stimulators TNF-alpha/IL-6. Vanadium compounds induced binding of PPAR gamma to heat shock protein (Hsp60). This PPAR gamma-Hsp60 interaction might cause inhibition of PPAR gamma degradation, thus elevating the PPAR gamma level. In addition, modulation of PPAR gamma phosphorylation was also observed upon vanadium treatment. The present work demonstrated for the first time that vanadium compounds are novel PPAR gamma modulators. The results may provide new insights for the mechanism of anti-diabetic action of vanadium compounds.