Possible involvement of transient receptor potential channels in electrophile-induced insulin secretion from RINm5F cells.

Abstract:

: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 Ca(2+) concentration and subsequent insulin secretion in a concentration-dependent manner. The increase in intracellular Ca(2+) concentration seemed to be due to an influx through the L-type voltage-dependent Ca(2+) channel, since it was not observed when extracellular Ca(2+) was absent and was inhibited almost completely by diltiazem or nifedipine. Ruthenium red, a non-specific inhibitor of TRP channels, inhibited the Ca(2+) 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-Δ(12,14)-prostaglandin J(2), significantly induced Ca(2+) 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 Ca(2+) influx via the activation of TRP channels, including TRPA1, which appears to be coupled with the L-type voltage-dependent Ca(2+) channel, and ultimately insulin secretion in RINm5F cells.

journal_name

Biol Pharm Bull

authors

Numazawa S,Takase M,Ahiko T,Ishii M,Shimizu S,Yoshida T

doi

10.1248/bpb.35.346

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

346-54

issue

3

eissn

0918-6158

issn

1347-5215

pii

JST.JSTAGE/bpb/35.346

journal_volume

35

pub_type

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