2004 Fiscal Year Final Research Report Summary
Study on a network of gut signals and development of diabetes
| Project/Area Number |
13204042
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
YAMADA Yuichiro Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (60283610)
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| Project Period (FY) |
2000 – 2004
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| Keywords | GIP / Incretin / knockout mouse / diabetes / obesity / osteoporosis / SNP |
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| Research Abstract |
Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat.. Our studies revealed that GIP receptor knockout mice have higher blood glucose levels with impaired initial insulin response after oral glucose load., that GIP receptor knockout mice fed a high-fat diet were clearly protected from both the obesity and the insulin resistance, that the insulin response was almost completely lost in Kir6.2 and GIP receptor double knockout mice, and that bone formation parameters in the GIP receptor knockout mice were significantly lower and the GIP receptor knockout mice had thinner trabeculae. These results and the in vitro studies that GIP directly acts not onlypancreatic b-cells but also adipocytes and osteoblasts indicated that early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load, that GIP directly links overnutrition to obesity, that GIP is the major insulinotropic factor in the secretion of insulin in response to glucose load in KATP channel-deficient mice, and that GIP directly links calcium contained in meal to calcium deposition on bone.
Therefore, GIP signaling should be activated by GIP receptor agonists or DPPIV inhibitors in diabetes with impaired insulin secretion, such as predominantly observed in Japan, and should be inhibited by GIP receptor antagonists in diabetes with insulin resistance, such as predominantly observed in western countries.
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Research Products
(108 results)
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[Patent(Industrial Property Rights)] インスリン抵抗性及び/又は肥満の予防剤もしくは改善剤2001
Inventor(s)
清野裕, 宮脇一真, 山田祐一郎, 坂信広, 鍔本義治, 武田基弘, 橋本洋幸, 山下篤行, 城森孝仁
Industrial Property Rights Holder
清野裕, 宮脇一真, 山田祐一郎, 坂信広, 鍔本義治, 武田基弘, 橋本洋幸, 山下篤行, 城森孝仁
Industrial Property Number
特願2001-144416
Filing Date
2001-05-15
Description
「研究成果報告書概要(和文)」より
