2003 Fiscal Year Final Research Report Summary
Analysis of inslin secretion insufficiency in type 2 diabetes due to calpain 10 dysfunction
| 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)
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| Project Period (FY) |
2001 – 2003
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| Keywords | susceptibility gene to type 2 diabetes / calpain-10 / microarray / SNPs / association study |
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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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Research Products
(14 results)
