| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
To study the role of vaspin, we generated vaspin transgenic (Tg) mice and vaspin knockout (KO) mice. Under high fat-high sucrose diet, the obesity, insulin resistance and fatty liver were ameliorated in Tg mice, while they were exacerbated in KO mice. We identified GRP78 as a vaspin-interacting molecule, and GRP78 forms complex with anchor proteins on the plasma membrane. On hepatocytes, vaspin interacts with GRP78/MTJ-1 complex and enhance the phosphorylation of Akt and AMPK, and improves glucose and lipid metabolism. Next, we studied the role of vaspin on atherosclerosis. Vaspin inhibited arterial intimal thickening of balloon injured and cuff-injured vessels of rodent model. Vaspin binds to GRP78/VDAC complex on vascular endothelial cells and competes with the known VDAC ligand, kringle 5. Vaspin inhibits kringle 5-induced apoptosis pathway and enhances the phosphorylation of Akt. Subsequently, vaspin inhibits apoptosis of vascular endothelial cells.
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