| Project/Area Number |
13470223
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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 | GUNMA UNIVERSITY |
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Principal Investigator |
HORIKAWA Yukio Gunma University, Inst.Mol.Cell.Reg., Associate Professor, 生体調節研究所, 助教授 (10323370)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Jun Gunma University, Inst.Mol.Cell.Reg., Professor, 生体調節研究所, 教授 (40270855)
戸村 秀明 群馬大学, 生体調節研究所, 助手 (70217553)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2001: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | susceptibility gene to type 2 diabetes / calpain-10 / microarray / SNPs / association study / 関連解析 / アデノウィルス / 連鎖不平衡マッピング |
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| Research Abstract |
As the main cause of type 2 diabetes in Japanese is the decrease in insulin secretion, this study was focused on the function of calpain-10 in pancreatic β cells, and was aimed at solving the mechanism of how calpain-10 abnormality induces decreased insulin secretion.
1.Clinical and metabolic analyses of two populations of completely different genetic background revealed that calpain-10 influences both secretion and action of insulin. Furthermore, by statistically analyzing variations of calpain-10 gene in multiple populations, we have shown that this gene had been naturally selected and suggested that it might be a thrifty gene. Identification of the mutation P200T of this gene which is specific in Japanese revealed the importance of investigating rare alleles when considering the genetic heterogeneity among different populations.
2.As calpain-10 is a processing protein expressed in multiple tissues, it is considered that several target substrates or calpain-10 associated molecules might cooperate with calpain-10 in the process of inducing type 2 diabetes.
Therefore, we planned to obtain as many of these molecules as possible and are now working on it with our collaborators using BIA‥MS/MS. In order to investigate the function of calpain-10 in vivo, we succeeded in generating transgenic mice that express approximately 40 to 100 times as much calpain-10 in pancreatic β cells as wild strains. We have also generated calpain-10 knock-out mice, and using islets isolated from these mice have shown that calpain-10 plays a part in fat-induced apoptosis via RyR2, suggesting the possibility of it's involvement in the exhaustion of pancreatic β cells.
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