2002 Fiscal Year Final Research Report Summary
Study for Diabetogenic Property of Mutant Amylin (S20G)
| Project/Area Number |
13671198
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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 | Wakayama Medical University |
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Principal Investigator |
SANKE Tokio Medicine Professor, 医学部, 教授 (20187305)
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| Co-Investigator(Kenkyū-buntansha) |
FURUTA Machi Medicine Associate Professor, 医学部, 講師 (00347585)
TSUNODA Keiko Medicine Assistant Professor, 医学部, 助手 (80233063)
NALAMINE Kazuhiro Medicine Associate Professor, 医学部, 講師 (70155810)
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| Project Period (FY) |
2001 – 2002
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| Keywords | type 2 Diabetes / Amyloid / Amylin / IAPP / β-cell |
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| Research Abstract |
Amylin is a peptide cosecreted with insulin from islet cells of the pancreas, and is a main constituent of islet amyloid deposits seen in type 2 diabetic patients. We found a missense mutation of the amylin gene (S20G) in Japanese patients with type 2 diabetes (frequence : 2-3 %). In order to clarify the possible diabetogenic property of the mutant amylin (Gly20-amylin) we studied the amyloidogenic property and cell toxicity of the mutant amylin. In the present study, we demonstrated that synthetic mutant amylin formed more amyloid than WT human amylin in vitro. Electron micrography indicated that amyloid produced by WT and mutant amylins were morphologically indistinguishable. We also demonstrated that mutant amylin, when expressed in COS1 cells, has severer apoptotic effects than WT human amylin by using fluorescent-activated cell sorting analysis. These results indicate that increase cytotoxicity of the mutant amylin is because of increased amyloidogenicity, which may be a causative factor in the early development of type 2 diabetes, the characteristic phenotype of the patients with mutant amylin gene, possibly through loss of beta cell mass. To vertify this hypothesis, we tried to make knock-in mice carrying mutant amylin or WT human amylin instead of mouse amylin gene, and we succeeded to get ES cell clones containing mutant or WT amylin gene constract. Using these clones we have now gotten chimera mice. These mice should be useful model for studying the possible mechanism for diabetogenic property of the mutant amylin.
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Research Products
(6 results)
