| Project/Area Number |
15580105
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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 |
Food science
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| Research Institution | Chubu University (2004)
Nagoya University (2003) |
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Principal Investigator |
HORIO Fumihiko Chubu University, College of Bioscience & Biotechnology, Professor, 応用生物学部, 教授 (20165591)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Masahiko Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20073661)
IKEGAMI Hiroshi Osaka University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20221062)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Type 2 diabetes / Disease gene / QTL analysis / High-fat diet / Nutritional Biochemistry / Genetics / 糖尿病モデルマウス / 糖尿病遺伝子 |
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| Research Abstract |
The SMXA-5 mouse is one of the 26 SMXA recombinant inbred (RI) substrains that have been established from nondiabetic SMIJ and A/J strains. This mouse is a model for polygenic type 2 diabetes characterized by both moderate impairment of glucose tolerance and mild hyperinsulinemia. To dissect A/J-derived diabetogenic loci of SMXA-5 contributing to diabetes-related traits such as impaired glucose tolerance, hyperglycemia, hyperinsulinemia, and obesity, we attempted to analyze the quantitative trait loci (QTL) in (SM/J x SAM-5)F2 intercross mice fed a high-fat diet. A major QTL for body mass index, nonfasting blood glucose concentration, and glucose tolerance was mapped on Chr 2. This locus existed near D2Mit15, with the highest logarithm of odds (LOD) score, 12.5, for glucose concentration being recorded at 120 min in an intraperitoneal glucose tolerance test (IPGTT). We designated this QTL as t2dm2sa, for type 2 diabetes mellitus 2 in the SMXA RI strains. SM.A-t2dm2sa, a congenic strain that introgressed the A/J-derived t2dm2sa region into SM/J, exhibited overt impaired glucose tolerance and mild hyperinsulinemia under a high-fat diet. These results suggested that latent diabetogenic genes exist in the genomes of nondiabetic AM and SM/J mice, and that interaction between t2dm2sa and an unknown SM/J-derived locus except where t2dm2sa exists, elicits impaired glucose tolerance in SMXA-5 and SM.A-t2dm2sa mice. The dissection of these diabetogenic genes that have epistatic effects will contribute to the elucidation of the complex mechanisms underlying human type 2 diabetes.
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