Regulation of AP-1 activity in glucose-stimulated insulinoma cells

The transcriptional activity of AP-1 has been analyzed in glucose-stimulated INS-1 insulinoma cells using a chromosomally embedded AP-1-responsive reporter gene. We show that AP-1 activity was significantly elevated in glucose-treated INS-1 cells. Preincubation of the cells with nifedipine or expression of the Ca(2+) binding protein parvalbumin in the cytoplasm of INS-1 cells reduced AP-1 activity. Thus, activation of L-type Ca(2+) channels and an elevated cytoplasmic Ca(2+) concentration are crucial to connecting glucose stimulation with enhanced AP-1 activity. Expression of dominant negative forms of A-Raf, MKK4 or MKK6 and pharmacological inhibition of MEK and p38 revealed that extracellular signal-regulated protein kinase, p38 and c-Jun NH(2)-terminal protein kinase participate in the upregulation of AP-1 activity. Expression of dominant-negative mutants of c-Jun and Elk-1 reduced AP-1 transcriptional activity in INS-1 cells indicating that c-Jun and ternary complex factors are involved in the regulation of AP-1 activity in glucose-stimulated insulinoma cells.