2004 Fiscal Year Final Research Report Summary
Molecular mechanism of lipotoxicity Functional analysis by adnovirus OBORb and PPARa
| Project/Area Number |
14571103
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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 | University of the Ryukyus |
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Principal Investigator |
SHIMABUKURO Michio University of the Ryukyus, Second Department of Internal Medicine, Assistant Professor, 医学部附属病院, 講師 (60271144)
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| Project Period (FY) |
2002 – 2004
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| Keywords | diabetes mellitus / insulin / leptin |
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| Research Abstract |
1.In pancreatic β cell line(INS-1), a model for lipotoxicity was constructed using OBRb mutant ZDF rat and high fat fed rat.
2.Molecular mechanism for cell death and survival signals in pancreatic b-cell lipotoxicity was clarified. Methods : After 1 rat insulinoma INS-1 cells with or without expression of dominant-negative mutant of Akt (K179M) were cultured with palmitate (C16:0) or oleate (C18:1), and cell numbers were determined by 0.2% eosin dye exclusion assay. The Akt activity was determined by anti-30-phospho-inositide-dependent protein kinase (Akt)/protein kinase B(PKB) or anti-phospho-Akt (Serine 473) immunoblotting, and nuclear protein nuclear factor-kB(NF-kB)-binding activity was by supershift analysis. Results : Twenty-four hours treatment with palmitate increased cell number INS-1 at 0.1-0.2mM but decreased at 0.5-1mM. Oleate did not affect cell number at 0.1-1.0mM. Palmitate dose-dependently increased.
phosphorylation of 473th serine in Akt/PKB. The K179M form of Akt/PKB abolished palmitate-induced cell proliferation at the low dose and death at the high dose. Nuclear protein NF-kB binding was enhanced at 0.2 and 0.5mM of palmitate but decreased at 1.0mM.
Conclusion : Results suggest that Akt/PKB signalling is involved in palmitate-induced cell death and survival of pancreatic b cell.
3.A model for lipotoxicity was constructed by coinfusion of intralipid/heparin to normal rats. Insulin sensitivity and endothelial function of the model was comapared with obese Zucker Diabetic Fatty rats (fa/fa).
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[Book] 糖尿病学2005
Author(s)
島袋充生(共著)
Publisher
西村書店(印刷中)
Description
「研究成果報告書概要(和文)」より
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