| Project/Area Number |
06671042
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
ARAKI Eiichi SCHOOL OF MEDICINE,RESEARCH ASSOCIATE Kumamoto University, 医学部, 助手 (10253733)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIKAWA Hideki SCHOOL OF MEDICINE,LECTURER Kumamoto University, 医学部, 講師 (30161441)
SHICHIRI Motoaki SCHOOL OF MEDICINE,PROFESSOR Kumamoto University, 医学部, 教授 (00028515)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Insulin receptor substrate-1 (IRS-1) / Non-insulin-dependent diabetes mellitus (NIDDM) / Genetics / Single strand conformation polymorphism (SSCP) / Insulin resistance / インスリン非依存型糖尿病 / インスリン受容体 / 糖尿病 / IRS-1 / ポリモルフィズム |
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| Research Abstract |
The results are summarized as follows.
1.PCR-SSCP analysis : The entire coding region of IRS-1 gene of 94 subjiects (47 NIDDM and 47 controls) was screened by PCR-SSCP analysis, and seven SSCP polymorphisms were identified.
2.Sequence analysis : By sequence analysis, 4 missense and 3 silent mutations corresponding to each SSCP polymorphisms were determined. Five polymorphisms {P170R,M209T,S809F,Leu^<142> (CTT*CTC), Gly^<625> (GGC*GGT) } were novel and two were previously reported {Ala^<804> (GCA*GCG), G971R}.
3.Evaluation of contribution of the IRS-1 gene polymorphisms to the development of insulin resistance : The prevalence of the four IRS-1 missense mutations taken together was significantly higher in NIDDM than that in control (23.4%vs.8.5%, P<0.05), and two missense mutations (M209T,S809F) were found only in NIDDM.The equilibrated glucose infusion rates (GIRs) during an euglycemic clamp in NIDDM and controls with the IRS-1 polymorphisms decreased by 29.5%and 22.0%, respectively in average when compared to those in comparable groups without polymorphisms, although they were not statistically significant probably due to the small number of subjects studied.
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