title: Hydrogen peroxide inhibits insulin-induced ATP-sensitive potassium channel activation independent of insulin signaling pathway in cultured vascular smooth muscle cells.
abstract: Both reactive oxygen species (ROS) and insulin resistance have been reported to play essential pathophysiological roles in cardiovascular diseases, such as hypertension and atherosclerosis. However, the mechanistic link between ROS and insulin resistance in the vasculature remains unclear. Recently we have shown that insulin causes membrane hyperpolarization via ATP-sensitive potassium (K(ATP)) channel activation, which is mediated by phosphatidylinositol 3-kinase (PI3-K) in cultured vascular smooth muscle cells (VSMCs). K(ATP) channel in the vasculature is critical in the regulation of vascular tonus. Here we examined the effects of ROS induced by hydrogen peroxide (H(2)O(2)) on insulin-induced K(ATP) channel activities in cultured VSMCs, A10 cells. H(2)O(2) (10 µM) increased significantly intercellular ROS in A10 cells. By using a cell-attached patch clamp experiment, 10 µM H(2)O(2) suppressed significantly insulin-induced K(ATP) channel activation without inhibition of insulin receptor signal transduction component including IRS and Akt in A10 cells. Furthermore 10 µM H(2)O(2) suppressed significantly pinacidil-induced K(ATP) channel activation in A10 cells. These data suggest that H(2)O(2) might inhibit directly K(ATP) channel independent of insulin signaling pathway. This study may contribute to our understanding of mechanisms of insulin resistance-associated cardiovascular disease.
authors.affiliation: Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Yasui
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Ran
authors.initials: R
authors.lastname: Morizumi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Takaaki
authors.initials: T
authors.lastname: Shimohata
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D016877:Oxidants; D006861:Hydrogen Peroxide