| Project/Area Number |
14571102
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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 | Oita University (2004)
大分医科大学 (2002-2003) |
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Principal Investigator |
HAMAGUCHI Kazuyuki OITA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (60180931)
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| Co-Investigator(Kenkyū-buntansha) |
INA Keisuke OITA UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (20203193)
WAKANA Sigeharu RIKEN GENOMIC SCIENCES CENTER, MOUSE FUNCTIONAL GENOMICS RESEARCH GROUP, TEAM LEADER, 研究員 (90192434)
YOSHIMATSU Hironobu OITA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (00166993)
加隈 哲也 大分医科大学, 医学部, 助手 (80343359)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | pancreatic α cell / glucagon / type 1 diabetes mellitus / type 2 diabetes mellitus / IKBL / HLA / anti-GAD antibody / SNP / マウス / 膵β細胞 / MIN6 / 糖尿病 / ゲノム / BRG1 / カルモジュリン / 転写因子 |
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| Research Abstract |
Complementary DNA of BRG1 (β related gene 1) has been isolated from the mouse pancreatic β cell-line (MIN6) which shows high level of BRG1 expression. In the research theme-1, rabbit polyclonal antibody against synthetic BRG1 peptides was obtained. Using this antibody, we examined the cellular localization of BRG1 protein in the pancreatic islet of mouse model for type 2 diabetes, db/db. Light-microscopic immunofluorescent staining for BRG1 protein revealed the cellular topography in the pancreatic a cells but not β, δ, or PP cells. Other non-endocrine tissues, i.e., liver and kidney, did not show any staining for BRG1 antibody. Immunoelectron microscopy revealed that the co-localization of BRG1 protein in the glucagon-granule in the pancreatic a cells. We assume that the pancreatic β cell line may de-differentiate to express protein which is normally expressed in the pancreatic α cells. BRG1 may be a unique protein which is colocalized in the glucagon granule of pancreatic α cells.
In
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the research theme-2 and theme-3, we carried out the genetic analysis of the genes which are etiologically related to diabetes. We obtained the genomic DNA samples from type 1 diabetic patients, GAD antibody-positive or negative type 2 diabetic patients, and normal control subjects. In the research theme-2, we investigated polymorphisms of inhibitor of κB-like (IKBL ; also known as"NFKBIL1") gene which is reported the association to cellular apoptosis and locates in the class III region of HLA complex. The results indicated a possible independent association between type 1 diabetes and SNPs in the promoter of the IKBL gene. In the research theme-3, we conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. The data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes. Less
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