| Project/Area Number |
14571082
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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 |
Metabolomics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
HIRAI Masashi Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (80312578)
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| Co-Investigator(Kenkyū-buntansha) |
KATAGIRI Hideki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00344664)
HINOKIO Yoshinori Tohoku University, Hospital, Lecturer, 医学部附属病院, 講師 (10282071)
SUZUKI Susumu Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70216399)
ISHIHARA Hisamitu Tohoku University, Hospital, Research Associate, 医学部附属病院, 助手 (60361086)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Type 2 diabetes mellitus / GPI specific phospholipase D / impairment of insulin secretion / insulin resistance / inositol glycan |
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| Research Abstract |
Glycosylphosphatidylinositol(GPI)-specific phospholipase D(GPI-PLD) cleaves GPI anchor and produces inositol glycan, which is thought to be a second messenger of insulin action. GPI-PLD also has been reported to be involved in insulin secretion. Thus, genetic variations of GPI-PLD could cause diabetes mellitus. Gene analysis was performed in type 2 diabetic patients (DM), the subjects with impaired glucose tolerance (IGT), and the subjects with normal glucose tolerance (NGT). There were totally six mutations resulting in amino acid replacement in exon 1,11,21,22. There are three haplotype alleles according to the combination of Leu/Val polymorphism in the 17th amino acid and Val/Leu in 30th amino acid in exon 1. The frequency of haplotype allele was significantly different among the three groups. The frequency of the mutant type allele was significantly higher in DM and IGT compared to NGT. The analysis of HOMAC (β) using NGT suggested that the subjects with the mutant allele had lower insulin secretary capacity compared to those with the wild type allele. The state of diabetic complications and therapies tended to be different according to the haplotype alleles. To examine the role of GPI-PLD in insulin secretion, we have suppressed the expression of GPI-PLD in insulin secreting cells (INS-1 cells) by introducing synthesized RNAi oligonucleotide and adenovirus RNAi. Furthermore, we have constructed cell lines expressing high levels of GPI-PLD by adenovirus expression vector. It is suggested that genetic variation of GPI-PLD was associated with diabetes us in Japanese due to the decreased insulin secretary capacity.
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