The PI3-K/Akt pathway : roles related to alterations in vasomotor responses in diabetic models
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概要
- 論文の詳細を見る
Macro- and microvascular disease states currently represent the principal causes of morbidity and mortality in patients with type I or type II diabetes mellitus. Abnormal vasomotor responses and impaired endothelium-dependent vasodilation have been demonstrated in various beds in different animal models of diabetes and in humans with type I or type II diabetes. Several mechanisms leading to endothelial dysfunction have been reported, including changes in substrate avail ability, impaired release of NO, and increased destruction of NO. The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals.
- 日本平滑筋学会の論文
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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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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