Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Possible Involvement of Transient Receptor Potential Channels in Electrophile-Induced Insulin Secretion from RINm5F Cells
Satoshi NumazawaMakiko TakaseTomomi AhikoMasakazu IshiiShun-ichi ShimizuTakemi Yoshida
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2012 Volume 35 Issue 3 Pages 346-354


Endogenously produced reactive oxygen species reportedly stimulate insulin secretion from islet β-cells. However, the molecular machinery that governs the oxidant-induced insulin secretion has yet to be determined. The present study demonstrates, using rat islet β-cell-derived RINm5F cells, the involvement of the transient receptor potential (TRP) cation channels in the insulin secretion induced by the lipid peroxidation product 4-hydroxy-2-nonenal. Short-term (1 h) exposure of 4-hydroxy-2-nonenal induced a transient increase in intracellular Ca2+ concentration and subsequent insulin secretion in a concentration-dependent manner. The increase in intracellular Ca2+ concentration seemed to be due to an influx through the L-type voltage-dependent Ca2+ channel, since it was not observed when extracellular Ca2+ was absent and was inhibited almost completely by diltiazem or nifedipine. Ruthenium red, a non-specific inhibitor of TRP channels, inhibited the Ca2+ influx and insulin secretion evoked by 4-hydroxy-2-nonenal. Among the TRP channels, TRPA1 was found to be predominantly expressed, not only in RINm5F cells, but also rat islets. TRPA1 agonists, allylisothiocyanate and 15-deoxy-Δ12,14-prostaglandin J2, significantly induced Ca2+ influx, and a specific inhibitor TRPA1, HC-030031, blocked the effects elicited by 4-hydroxy-2-nonenal. These results suggest that 4-hydroxy-2-nonenal induces Ca2+ influx via the activation of TRP channels, including TRPA1, which appears to be coupled with the L-type voltage-dependent Ca2+ channel, and ultimately insulin secretion in RINm5F cells.

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© 2012 The Pharmaceutical Society of Japan
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