Investigation for intracellular mechanisms of pancreatic-cell proliferation and anti-apoptotic effect of incretin

胰腺细胞增殖的细胞内机制及肠促胰岛素抗凋亡作用的研究

• 批准号: 21591132
• 负责人: SEINO Yutaka
• 金额: $ 2.83万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591132/
• 关键词: エネルギー; 糖質代謝異常; インクレチン; アポトーシス; ERストレス; CHOP; Bip; XBP-1

Endoplasmic reticulum stress(ERS) is one of the contributing factors in the development of type 2 diabetes. Exendin-4(Ex-4), a potent GLP-1 receptor agonist, significantly reduced blood glucose levels and preservedυ-cell mass and the number of islets in Akita mice, an animal model of ER stress-mediated diabetes. Since there was no such effect observed in the mice treated with phlorizin, an insulin-independent glucose-lowering drug, the effects were suggested to be independent of glucose-lowering effect of Ex-4. Akita mice treated with Ex-4 showed a significant decrease in apoptosis ofυ-cells and significantly reduced CHOP mRNA and protein levels inυ-cells, suggesting thatυ-cell protective effects of Ex-4 were achieved mainly through a reduction of ER stress-mediatedυ-cell damage and apoptotic cell death.

内质网应激（ERS）是2型糖尿病发生发展的重要因素之一。毒蜥外泌肽-4（Ex-4），一种有效的GLP-1受体激动剂，显著降低了秋田小鼠（ER应激介导的糖尿病动物模型）的血糖水平，并保留了胰岛细胞质量和胰岛数量。由于在用根皮苷（一种胰岛素非依赖性降糖药物）处理的小鼠中未观察到这种作用，因此认为该作用与Ex-4的降糖作用无关。用Ex-4处理的秋田小鼠显示出ER-细胞凋亡的显著减少和ER-细胞中CHOP mRNA和蛋白水平的显著降低，表明Ex-4的ER-细胞保护作用主要通过减少ER应激介导的ER-细胞损伤和凋亡性细胞死亡来实现。

项目成果

GLP-1アナログによるAkitaマウスの小胞体ストレス減少効果

GLP-1类似物减轻秋田小鼠内质网应激的作用

• 发表时间: 2009
• 作者: 山根俊介;浜本芳之;原田範雄;豊田健太郎;清野裕;稲垣暢也
• 通讯作者: 稲垣暢也

Evaluation of the effect of GLP-1 receptor activation on ER stress mediated beta cell damage in Akita mice

GLP-1受体激活对秋田小鼠内质网应激介导的β细胞损伤的影响评估

• 发表时间: 2010
• 作者: Kawashima S;Matsuoka T;Kaneto H;Tochino Y.;Kato K;Yamamoto K;Yamamoto T;Matsuhisa M;Shimomura I.;Fujisaka S.;山根俊介
• 通讯作者: 山根俊介

LP-1アナログによるAkitaマウスの小胞体ストレス減少効果

LP-1类似物减轻秋田小鼠内质网应激的作用

• 发表时间: 2009
• 作者: 山根俊介;原田範雄;山田千積;豊田健太郎;浜本芳之;清野裕;稲垣暢也
• 通讯作者: 稲垣暢也

Exendin-4 Protects Pancreatic Beta Cells from the Cytotoxic Effect of Rapamycin by Inhibiting JNK and p38 Phosphorylation

• DOI: 10.1055/s-0030-1249035
• 发表时间: 2010-05-01
• 期刊: HORMONE AND METABOLIC RESEARCH
• 影响因子: 2.2
• 作者: Kawasaki, Y.;Harashima, S.;Inagaki, N.
• 通讯作者: Inagaki, N.

The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

• DOI: 10.1016/j.bbrc.2010.11.077
• 发表时间: 2011-01-07
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ogawa, Eiichi;Hosokawa, Masaya;Inagaki, Nobuya
• 通讯作者: Inagaki, Nobuya