The pH dependence of interleukin-1 beta effects on insulin secretion in HIT cells

We have examined a hypothesis that the effects of recombinant human interleukin-1 beta (IL-1) on insulin secretion may depend upon the condition of intracellular pH levels in hamster clonal beta-cell line, HIT-T 15 cells. In the first experiment, the addition of 5 and 20 microM monensin, a Na+/H+ electroneutral exchange ionophore, did not attenuate a short-stimulatory effect of IL-1 on insulin secretion at 0-4 h period. At the concentration of 20 microM, monensin deleted the IL-1-induced reduction of insulin secretion at 4-24 h period, while 5 microM did not. Furthermore, 100 microM monensin blocked the bimodal effects of IL-1 on insulin secretion. In the second experiment, IL-1 significantly stimulated insulin secretion, although it did not affect cyclic AMP production at 0-4 h period. At 4-24 h period, IL-1 dose-dependently inhibited cyclic AMP production, accompanied with a significant reduction of insulin secretion. Alkalinization of circumstantial pH levels to 8.0 deleted the IL-1 effects on insulin secretion at 4-24 h period. However, alkalinization to pH 8.0 failed to attenuate the reduction of cyclic AMP production by IL-1. These data indicated that maintaining adequate intracellular pH levels may be important in the IL-1 effects on insulin secretion by the mechanism in which cyclic AMP may not be involved.