| Project/Area Number |
16390262
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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 |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ASANO Tomoichiro The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (70242063)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKUDA Katsunori The University of Tokyo, Hospital, Medical Staff, 医学部附属病院, 医員
FUJISHIRO Midori The University of Tokyo, Hospital, Medical Staff, 医学部附属病院, 医員 (50420211)
ABE Miho The University of Tokyo, Hospital, Medical Staff, 医学部附属病院, 医員
SHOJIMA Nobuhiro The University of Tokyo, Hospital, Medical Staff, 医学部附属病院, 医員
KUSHIYAMA Akifumi The University of Tokyo, Hospital, Medical Staff, 医学部附属病院, 医員
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | insulin / Akt / Diabetes mellitus / insulin resistance / resistin / AMPK / 運動 / 糖輸送担体 |
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| Research Abstract |
Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were identified and given the names resistin-like molecules (RELM) α, β and γ. Resistin and RELMα are abundantly expressed in adipose, but RELMβ and RELMγ are secreted mainly from the gut. Since nutrient composition greatly affects insulin sensitivity, we investigated the regulatory effects of various nutritional factors in food on the expressions of resistin family proteins.
First, mice were given diets with different nutritional compositions (high-carbohydrate, high-protein and high-fat) for two weeks. RELMβ mRNA expression in the intestines was markedly suppressed by the high-protein and high-carbohydrate diets, while slightly but not significantly upregulated by the high-fat diet. In the epididymal fat, resistin expression was unchanged, while RELMβ expression was markedly decreased by the high-carbohydrate diet. Taking into consideration that humans have neither RELMα nor RELMγ, our subsequent studies focused on RELMβ expression. We used the human colon cancer cell line LS174T. Treatments with insulin and TNFα as well as stearic acid, a saturated free fatty acid, upregulated RELMβ expression, while D-glucose downregulated RELMβ. These results suggest RELMβ expression to be regulated directly by nutrients such as glucose and saturated free fatty acids including stearic acid, as well as by hormones including insulin and TNFα. These regulations may play an important role in the nutrient-associated induction of insulin resistance.
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