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- Title
Insulin Activates ATP-Sensitive Potassium Channels via Phosphatidylinositol 3-Kinase in Cultured Vascular Smooth Muscle Cells.
- Authors
Yasui, Sonoko; Mawatari, Kazuaki; Kawano, Takashi; Morizumi, Ran; Hamamoto, Akiko; Furukawa, Hiroko; Koyama, Kei; Nakamura, Aki; Hattori, Atsushi; Nakano, Masayuki; Harada, Nagakatsu; Hosaka, Toshio; Takahashi, Akira; Oshita, Shuzo; Nakaya, Yutaka
- Abstract
The effects of insulin on the vasculature are significant because insulin resistance is associated with hypertension. To increase the understanding of the effects of insulin on the vasculature, we analyzed changes in potassium ion transport in cultured vascular smooth muscle cells (VSMCs). Using the potential-sensitive fluorescence dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)], we found that insulin induced membrane hyperpolarization after 2 min in A10 cells. Insulin-induced hyperpolarization was suppressed by glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. Using a cell-attached patch clamp experiment, the KATP channel was activated by insulin in both A10 cells and isolated VSMCs from rat aortas, indicating that insulin causes membrane hyperpolarization via KATP channel activation. These effects were not dependent on intracellular ATP concentration, but wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, significantly suppressed insulin-induced KATP channel activation. In addition, insulin enhanced phosphorylation of insulin receptor, insulin receptor substrate (IRS)-1 and protein kinase B (Akt) after 2 min. These data suggest that KATP channel activation by insulin is mediated by PI3-K. Furthermore, using a nitric oxide synthase (NOS) inhibitor, we found that NOS might play an important role downstream of PI3-K in insulin-induced KATP channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated hypertension. Copyright © 2007 S. Karger AG, Basel
- Subjects
PHOSPHOINOSITIDES; INSULIN; ADENOSINE triphosphate; ADENINE nucleotides; POTASSIUM; SMOOTH muscle
- Publication
Journal of Vascular Research, 2008, Vol 45, Issue 3, p233
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000112545