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.
Shimizu
H
H
First Department of Internal Medicine, Gunma University School of Medicine, Japan.
Uehara
Y
Y
Sato
N
N
Mori
M
M
Shimomura
Y
Y
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D008985:Monensin; D000242:Cyclic AMP