Reactive oxygen species induced by diamide inhibit insulin-induced ATP-sensitive potassium channel activation in cultured vascular smooth muscle cells

Kazuaki Mawatari, Sonoko Yasui, Ran Morizumi, Akiko Hamamoto, Hiroko Furukawa, Kei Koyama, Atsushi Hattori, Emiko Yoshioka, Masaki Yoshida, Masayuki Nakano, Kiyoshi Teshigawara, Nagakatsu Harada, Toshio Hosaka, Akira Takahashi, Yutaka Nakaya

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Both insulin resistance and reactive oxygen species (ROS) have been reported to play essential pathophysiological roles in cardiovascular diseases. However, the mechanistic link between ROS and insulin resistance in the vasculature remains unclear. Recently we have shown that insulin causes K ATP channel activation mediated by PI3K in cultured vascular smooth muscle cells (VSMCs). KATP channel in VSMCs is critical in the regulation of vascular tonus. Here we examined the effects of ROS induced by a thol-oxidizing agent, diamide, on the insulin signalling pathway and K ATP channel activities in cultured VSMCs (A10 cells). Diamide (100 μM) increased intercellular ROS and extracellular signal-regulated kinases (ERK) activitiy. Treatment with 100 μM diamide suppressed significantly insulin-induced IRS and Akt phosphorylation. In addition to IRS and Akt, diamide inhibited insulin receptor auto-phosphorylation. Patch-clamp study showed that diamide suppressed insulin-induced but did not pinacidil-induced KATP channel activities in A10 cells. From these data, we conclude that ROS inhibit critical insulin signal transduction components including IRS and Akt, and these effects cause down-regulation of insulin's action in the vasculature including KATP channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated cardiovascular disease.

Original languageEnglish
Pages (from-to)162-166
Number of pages5
JournalAsia Pacific Journal of Clinical Nutrition
Volume17
Issue numberSUPPL. 1
Publication statusPublished - Jan 1 2008
Externally publishedYes

Keywords

  • Insulin
  • Oxidative stress
  • Potassium channel
  • Reactive oxygen species
  • Smooth muscle cells

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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  • Cite this

    Mawatari, K., Yasui, S., Morizumi, R., Hamamoto, A., Furukawa, H., Koyama, K., Hattori, A., Yoshioka, E., Yoshida, M., Nakano, M., Teshigawara, K., Harada, N., Hosaka, T., Takahashi, A., & Nakaya, Y. (2008). Reactive oxygen species induced by diamide inhibit insulin-induced ATP-sensitive potassium channel activation in cultured vascular smooth muscle cells. Asia Pacific Journal of Clinical Nutrition, 17(SUPPL. 1), 162-166.