TY - JOUR
T1 - Reactive oxygen species induced by diamide inhibit insulin-induced ATP-sensitive potassium channel activation in cultured vascular smooth muscle cells
AU - Mawatari, Kazuaki
AU - Yasui, Sonoko
AU - Morizumi, Ran
AU - Hamamoto, Akiko
AU - Furukawa, Hiroko
AU - Koyama, Kei
AU - Hattori, Atsushi
AU - Yoshioka, Emiko
AU - Yoshida, Masaki
AU - Nakano, Masayuki
AU - Teshigawara, Kiyoshi
AU - Harada, Nagakatsu
AU - Hosaka, Toshio
AU - Takahashi, Akira
AU - Nakaya, Yutaka
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
KW - Insulin
KW - Oxidative stress
KW - Potassium channel
KW - Reactive oxygen species
KW - Smooth muscle cells
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UR - http://www.scopus.com/inward/citedby.url?scp=46049104035&partnerID=8YFLogxK
M3 - Article
C2 - 18296327
AN - SCOPUS:46049104035
VL - 17
SP - 162
EP - 166
JO - Asia Pacific Journal of Clinical Nutrition
JF - Asia Pacific Journal of Clinical Nutrition
SN - 0964-7058
IS - SUPPL. 1
ER -
