Analysis of the mechanisms of pancreatic β-cells destruction by intra-cellular oxidative stress and endoplasmic reticulum stress, and its application for the diabetes treatment.
| Project/Area Number |
16390266
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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 | Kumamoto University |
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Principal Investigator |
ARAKI Eiichi Kumamoto University, Graduate School of Medical Sciences, Metabolic Medicine, Professor, 大学院・医学薬学研究部, 教授 (10253733)
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| Co-Investigator(Kenkyū-buntansha) |
TOYONAGA Tetsushi Kumamoto University, Graduate School of Medical Sciences, Metabolic Medicine, Assistant Professor, 大学院・医学薬学研究部, 助手 (60295128)
KONDO Tatsuya Kumamoto University, University Hospital, Metabolism and Endocrinology, Assistant Staff, 医学部附属病院, 医員 (70398204)
松本 和也 熊本大学, 医学部附属病院, 助手 (80346999)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | Diabetes Mellitus / Oxidative Stress / Endoplasmic Reticulum Stress / Pancreatic β-cell / ミトコンドリアROS / ERストレス / Mn-SOD / Bip |
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| Research Abstract |
Accumulating evidences suggest that intra-cellular oxidative stress and disturbance of endoplasmic function in pancreatic β-cells are new mechanisms of β-cell dysfunction. This study was undertaken to reveal the role of mitochondrial reactive oxygen species and endoplasmic reticulum stress in the pathogenesis of type 2 diabetes.
The mitochondrial reactive oxygen species was evaluated in the type 2 diabetic model mice (ob/ob and db/db) by immunohistochemical method. The expression of mitotracker red CC-1 (maker of mitochondrial biogenesis) was increased in the pancreas of diabetic mice. The endoplasmic reticulum stress was also evaluated in the pancreas of type 2 diabetic model mice by RT-PCR gene expression method. The expressions of endoplasmic reticulum stress related genes (Bip, PERK, Ire1α, Calnexin and Calreticulin) were increased when compared with those of non-diabetic control mice. The manganese superoxide dismutase transgenic mice and the Bip transgenic mice have been generated and now under investigation. These transgenic mice are useful for the in vivo analysis of mitochondrial reactive oxygen species and endoplasmic reticulum stress in the pathogenesis of type 2 diabetes.
These results suggest that mitochondrial biogenesis and endoplasmic reticulum stress are activated in the pancreatic β-cells of type 2 model mice.
This study suggests that the reactive oxygen species from mitochondria and endoplasmic reticulum stress are the new target for the treatment of type 2 diabetes.
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] Enhanced expression of PDX-1 and Ngn3 by exending-4 during β cell regeneration in STZ-treated mice.2005
Author(s)
Kodama S, Toyonaga T, Kondo T, Matsumoto K, Tsuruzoe K, Kawashima J, Goto H, Kume K, Kume S, Sakakida M, Araki E
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Journal Title
Biochem Biophys Res Commun 327
Pages: 1170-1178
Description
「研究成果報告書概要(欧文)」より
Related Report
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