| Project/Area Number |
11556024
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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 | 展開研究 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
HORIO Fumihiko Graduate School of Bioagricultural Sciences, Nagoya University, Associate Professor, 大学院・生命農学研究科, 助教授 (20165591)
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| Co-Investigator(Kenkyū-buntansha) |
IKEGAMI Hiroshi Osaka University Medical School, Assistant professor, 医学部, 助手 (20221062)
NISHIMURA Masahiko Nagoya University Medical School, Professor, 医学部, 教授 (20073661)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Diabetes / Glucose tolerance / QTL analysis / Disease model / Diabetogenic gene / 高インスリン血症 / 高血糖 / 糖糖能 / リコンビナント・インブレッド系統 / インスリン非依存型糖尿病 / 血糖値 / 肥満 |
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| Research Abstract |
Type 2 diabetes in humans is not a single gene disorder, but rather it is brought about by the interaction of multiple genes and environmental factors. Recombinant inbred (RI) strains are a powerful tool for analyzing not only single genetic traits, but also multifactorial genetic traits. By using the SMXA RI mice, we genetically dissected diabetes-related traits (BMI, non-fasting blood glucose concentration, and blood glucose concentration during IPGTT). In this study, all mice were fed the high-carbohydrate diet, because feeding this diet minimizes the variation of glucose tolerance in each strain. The parental strains, SM/J and A/J, were non-diabetic, and the differences of the mean values on diabetes-related traits were small. On the other hand, "notable differences" in the mean values of some diabetes-related traits were observed in 19 SMXA RI strains. Several SMXA RI strains showed distinct impaired glucose tolerance and hyperglycemia. QTL analysis revealed six diabetes-related loci on four chromosomes which exceeding the threshold for suggestive level. Especially, a locus on Chr 10 concerning non-fasting blood glucose concentration, was over significant threshold. The A/J-derived genome at two loci on Chr 2 and 18, oppositely the SM/J-derived genome at one locus on Chr 10, contributed to the impairment of glucose tolerance and/or the increase of blood glucose concentration. The present study indicate that the I combinations between silent SM/J and A/J allele can appear to elicit hyperglycemia and impaired glucose tolerance. Genetic dissection of this kind of diabetogenesis may contribute to understand the complex mode of inheritance in human type 2 diabetes.
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