title: Insulin activates ATP-sensitive potassium channels via phosphatidylinositol 3-kinase in cultured vascular smooth muscle cells.
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 (K(ATP)) channel blocker. Using a cell-attached patch clamp experiment, the K(ATP) channel was activated by insulin in both A10 cells and isolated VSMCs from rat aortas, indicating that insulin causes membrane hyperpolarization via K(ATP) channel activation. These effects were not dependent on intracellular ATP concentration, but wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor, significantly suppressed insulin-induced K(ATP) 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 K(ATP) 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 K(ATP) channel activation. This study may contribute to our understanding of mechanisms of insulin resistance-associated hypertension.
authors: Department of Nutrition and Metabolism, University of Tokushima Graduate School, Tokushima, Japan.
authors: Sonoko
authors: S
authors: Yasui
authors: Kazuaki
authors: K
authors: Mawatari
authors: Takashi
authors: T
authors: Kawano
authors: Ran
authors: R
authors: Morizumi
authors: Akiko
authors: A
authors: Hamamoto
authors: Hiroko
authors: H
authors: Furukawa
authors: Kei
authors: K
authors: Koyama
authors: Aki
authors: A
authors: Nakamura
authors: Atsushi
authors: A
authors: Hattori
authors: Masayuki
authors: M
authors: Nakano
authors: Nagakatsu
authors: N
authors: Harada
authors: Toshio
authors: T
authors: Hosaka
authors: Akira
authors: A
authors: Takahashi
authors: Shuzo
authors: S
authors: Oshita
authors: Yutaka
authors: Y
authors: Nakaya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D054086:KATP Channels; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt