Possible Involvement of Transient Receptor Potential Channels in Electrophile-Induced Insulin Secretion from RINm5F Cells

• Numazawa Satoshi

  Department of Biochemical Toxicology, Showa University School of Pharmacy

• Takase Makiko

  Department of Biochemical Toxicology, Showa University School of Pharmacy

• Ahiko Tomomi

  Department of Biochemical Toxicology, Showa University School of Pharmacy

• Ishii Masakazu

  Department of Pathophysiology, Showa University School of Pharmacy

• Shimizu Shun-ichi

  Department of Pathophysiology, Showa University School of Pharmacy

• Yoshida Takemi

  Department of Biochemical Toxicology, Showa University School of Pharmacy

抄録

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-Δ^12,14-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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 35 (3), 346-354, 2012

  公益社団法人 日本薬学会

キーワード

• 4-hydroxy-2-nonenal
• transient receptor potential channel
• islet
• voltage-dependent Ca²⁺ channel

詳細情報

• CRID: 1390001204631545728
• NII論文ID: 130001872315
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.35.346
• COI: 1:STN:280:DC%2BC383nvVWhuw%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 023439703
• PubMed: 22382320
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023439703
• Web Site: http://www.jstage.jst.go.jp/article/bpb/35/3/35_3_346/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012301675
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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