| Project/Area Number |
10672158
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
MURAKI Takamura Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (50051446)
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| Co-Investigator(Kenkyū-buntansha) |
IRIE Kaoru Tokyo Women's Medical University, School of Medicine, Research Associate, 医学部, 助手 (50075496)
FUJII Emiko Tokyo Women's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (20075493)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | advanced glycation endproducts / streptozotocin-diabetic mice / plasma extravasation / platelet activating factor / plasminogen activator inhibitor-1 / gene expression / endothelial cells / white adipocyte / 糖化最終産物 / 血管透過性 / 内皮細胞 / ストレプトゾトシン / セロトニン |
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| Research Abstract |
Hyperglycemia followed by the formation of advanced glycation endproducts (AGEs) is considered to be the major cause of vascular complications associated with diabetes. The following studies were performed to investigate the possible role of AGEs in the pathogenesis of diabetic vascular complications.
1). The effect of diabetes on plasma extravasation induced by proinflammatory agents was investigated in streptozotocin (STZ)-diabetic mice 2 weeka after STZ (170 mg/kg ip), using dye leakage method. The platelet activating factor (PAF)-induced increase in vascular permeability was inhibited in the STZ-diabetes mice. Normalization of blood glucose by insulin treatment restored the PAF-induced vascular peameability response to the level of normal controls. Aminoguanidine treatment, which is proposed to prevent the AGE formation, did not reverse the diminished response to PAF in the STZ-diabetic mice.
2). The effects of AGE-BSA and 3-deoxyglucoson (3-DG), an eary glycation product, were studied on various function of inflammatory cells, including albumin peameability through the monolayer of bovine endothelial cells, adhesion of monocytes on the human umbilical vein endothelial cells (HUVECs) and the chemotaxis of rat smooth muscle cells. These functions of cultured cells were not affected by incubation with 3-DG or AGE-BSA. When HUVECs were cultured in g;lycated collagen-coated dishes, cell proliferation was reduced.
3). The mRNA expression of plasminogen activator inhibitor (PAI)-1 was examined in cultured rat white adipocytes by northern blot analysis. AGE-BSA increased the PAI-1 mRNA abundance in white adipocytes concentration-dependently. Increase in blood PAI-1 induces thrombosis, thereby may cause the vascular complications in diabetes.
4). Although AGEs have significant effects on adipocytes, they did not disrupt the integrity of cultured endothelial cells.
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