2005 Fiscal Year Final Research Report Summary
Wnt signaling in aging related diseases
| Project/Area Number |
16390087
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
YAMAMOTO Tokuo Tohoku University, Institute of Development, Aging and Cancer, Professor, 加齢医学研究所, 教授 (30192412)
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| Co-Investigator(Kenkyū-buntansha) |
INAGAKI Yosuke Tohoku University, Institute of Development, Aging and Cancer, Research Associate, 加齢医学研究所, 助手 (60400412)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Wnt / cholesterol / hyperlipidemia / LRP5 / glucose tolerance / type 2 diabetes |
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| Research Abstract |
LRP5, one of LDLR-related proteins (LRPs), recognizes apoE-lipoproteins. LRP5-/- mice fed a high-fat diet, plasma cholesterol levels were significantly higher than those in wild-type mice and plasma clearance and hepatic uptake of chylomicron remnants are markedly reduced. These results indicate that LRP5 recognizes apoE-containing lipoproteins in vivo and plays a role in the hepatic clearance of chylomicron remnants. Furthermore, LRP5-/- mice exhibited markedly impaired glucose tolerance. These data indicated that LRP5 plays multiple functions in the normal adult including hepatic clearance of chylomicron remnants and stimulating glucose-induced insulin secretion from the islets. Impaired hepatic clearance of chylomicron remnants and glucose-induced insulin secretion lead to two disorders common in western countries : dietary-induced hypercholesterolemia and type 2-diabetes, respectively.
LRP5 and its closely related protein, LRP6, play a key role in Wnt signaling as co-receptors. To further define the molecular mechanisms underlying Wnt stimulated cholesterol clearance and glucose-induced insulin secretion, we have highly purified several wnt proteins and using these proteins we have characterized some wnt signaling in aging related diseases.
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