Effect of Insulin on Aortic Rings Isolated from Wistar Rats
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概要
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Background:Insulin increases nitric oxide (NO) production via the phosphatidylinositol 3-kinase(PI3K) pathway and endothelin( ET)-1 secretion via the mitogen-activated protein kinase( MAPK) pathwayin vascular endothelial cells. In normal vascular endothelial cells, the insulin effect via the PI3K pathwayis thought to occur slightly earlier than that via the MAPK pathway. However, the direct effect of insulinon vascular rings isolated from an animal model has not been fully examined. The main purpose of studywas to investigate the potential vasodilation-effect of insulin on the isolated vascular rings of rats.Material and Methods:Descending aorta rings isolated from Wister rats were used in exo-vivo study.In study using culture cells, bovine aortic endothelial cells were used, and the effect of insulin on the productionof nitric oxide( NO) and the secretion of endothelin( ET)-1 was investigated. NO production was evaluatingusing diaminofluorescein-2, a NO-specific dye.Results:Insulin (250 nM)-stimulated NO production evaluated using diaminofluorescein-2 (DAF-2) dependencyon the NO concentration in BAECs indicated a significant increase in NO compared with controls.Addition of 250 nM insulin also significantly increased ET-1 secretion and phosphorylation of Akt at Ser473and eNOS at Ser1177 (Ser1179 in bovine eNOS) in BAECs, compared with controls. Insulin treatmentshowed a slight tendency to increase phosphorylation of extracellular signal-regulated kinase (ERK) 1/2,but this change did not reach statistical significance. A cumulative insulin concentration of 3×10−6 M producedonly a small change in the diameter of aortic rings from Wister rats( 7.3±3.5% vs. 3.6±3.5% with 3×10−6 M saline;both n=3). Addition of acetylcholine to these rings caused dilatation of almost 100 %.Conclusion:Insulin increases production of NO and secretion of ET-1 in BAECs, but has little effect onaortic rings isolated from Wister rats.
- 2010-03-25
著者
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Kohzo Takebayashi
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital
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Ryouichi Sohma
Joint Research Center, Dokkyo Medical University Koshigaya Hospital
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Rika Naruse
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital
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Yoshimasa Aso
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital
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Toshihiko Inukai
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital
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Toshihiko Inukai
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Inukai Toshihiko
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Yoshimasa Aso
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Rika Naruse
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Ryouichi Sohma
Joint Research Center Dokkyo Medical University Koshigaya Hospital
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Kohzo Takebayashi
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Takebayashi Kohzo
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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Naruse Rika
Department Of Internal Medicine Dokkyo Medical University Koshigaya Hospital
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ASO YOSHIMASA
Department of Internal Medicine, Dokkyo Medical University Koshigaya Hospital
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Sohma Ryouichi
Joint Research Center, Dokkyo Medical University Koshigaya Hospital
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ASO Yoshimasa
Department of Endocrinology and Metabolism, Dokkyo Medical University
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