| Project/Area Number |
17590942
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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 | KUMAMOTO UNIVERSITY |
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Principal Investigator |
TSURUZOE Kaku KUMAMOTO UNIVERSITY, UNIVERSITY HOSPITAL, RESEARCH ASSOCIATES, 医学部附属病院, 助手 (50398202)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMURA Nobuhiro KUMAMOTO UNIVERSITY, UNIVERSITY HOSPITAL, LECTURERS, 医学部附属病院, 講師 (40274716)
NISHIDA Kenro K KUMAMOTO UNIVERSITY, UNIVERSITY HOSPITAL, RESEARCH ASSOCIATES, 医学部附属病院, 助手 (50336244)
TOYONAGA Tetsushi KUMAMOTO UNIVERSITY, FACULTY OF MRDICAL AND PHARMACEUTICAL SCIENCES, LECTURERS, 大学院医学薬学研究部, 講師 (60295128)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | pancreatic beta cell / insulin secretion / CaM kinase II |
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| Research Abstract |
Ca2+/calmodulin-dependent protein kinase II (CaM kinase 11)δ2 has been reported to be involved in the glucose induced insulin secretion possibly by the phosphorylation of synapsin I. However, the effect of prolonged activation that was induced by the long-term hyperglycemia in diabetes was not uncertain. The purpose of this study are to evaluate the role of CaM kinase II in the onset or progression of type 2 diabetes by analysis of transfect:.on of wild type or various mutated CaM kinase II 82 in pancreatic b cell line, MIN6 cells. At first, We constructed the expression vectors pCAGGSneo carrying WT CaMKII δ2 (WT), constitutive active form (ACT), kinase negative form (KD). Then, to determine if the observed to repress CREB dependent insulin promoter transcription that was due to CaMKII mutants, a series of luciferase reporter plasmids containing the insulin promoter and renila vector were co-transfected with these mutants into MIN6 cells using HilyMax transfection reagent. After stimulation by Glucose, these cells were harvested, and the cell lysates were subjected to luciferase assay.
When WT and ACT CaM kinase II were overexpressed under 5mM Glucose condition, these insulin promoter activities were decreased by 47%. and 53% respectively. Other way, KD CaM kinase II overexpression increased insulin promoter activity to 204%. These results suggest the possibility that insulin gene promoter activity and the expression of insulin gene are inhibited by the activation of CaM kinase II 82 via phosphorylation of Serine-133 and Serine-147 of CREB.
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