Possible Involvement of Akt Activity in Endothelial Dysfunction in Type 2 Diabetic Mice
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概要
- 論文の詳細を見る
We investigated the effects of chronic simvastatin treatment on the impaired endothelium-dependent relaxation seen in aortas from type 2 diabetic mice. Starting at 8 weeks of diabetes, simvastatin (10 mg/kg per day) was administered to diabetic mice for 4 weeks. The significantly elevated systolic blood pressure in diabetic mice was normalized by simvastatin. Aortas from diabetic mice, but not those from simvastatin-treated diabetic mice, showed impaired endothelium-dependent relaxation in response to both clonidine and adrenomedullin. After preincubation with an Akt inhibitor, these relaxations were not significantly different among the three Akt inhibitor–treated groups (controls, diabetics, and simvastatin-treated diabetics). Although clonidine-induced NOx− (NO2− + NO3−) production was greatly attenuated in our diabetic model, it was normalized by simvastatin treatment. The expression levels of both total Akt protein and clonidine-induced Ser-473-phosphorylated Akt were significantly decreased in diabetic aortas, while chronic simvastatin administration improved these decreased levels. The expression level of clonidine-induced phosphorylated PTEN (phosphatase and tensin homolog deleted on chromosome ten) was significantly increased in diabetic aortas, but chronic simvastatin did not affect it. These results strongly suggest that simvastatin improves the endothelial dysfunction seen in type 2 diabetic mice via increases in Akt and Akt phosphorylation.
- 社団法人 日本薬理学会の論文
- 2008-04-20
著者
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MATSUMOTO Takayuki
Departments of Laboratory Medicine, Ohashi and Omori Hospitals, School of Medicine, Toho University
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KAMATA Katsuo
Department of Pharmacology, School of Pharmacy, Hoshi University
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Kamata K
Dep. Of Physiology And Morphology Inst. Of Medicinal Chemistry Hoshi Univ.
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Kamata Katsuo
Department Of Pharmacology School Of Pharmacy Hoshi University:department Of Chemical Pharmacology F
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KOBAYASHI Tsuneo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University
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TAKENOUCHI Yasuhiro
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University
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Matsumoto Takayuki
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Kobayashi Tsuneo
Department Of Physiology And Morphology Institute Of Medicinal Chemistry Hoshi University
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Matsumoto Takayuki
Department Of Gastroenterology And Hepatology Institute Of Clinical Medicine Graduate School Of Comp
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Kobayashi Tsuneo
Department Of Physics School Of Medicine Fukushima Medical University
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Matsumoto Takayuki
Department Of Electronics Information And Communication Engineering Waseda University
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KAMATA Katsuo
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University
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KOBAYASHI TSUNEO
Department of Natural Sciences (Physics), School of Medicine, Fukushima Medical University
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KOBAYASHI Tsuneo
Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo Noko University
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