Pancreatic β cell impairment and adaptation of type 2 diabetes mellitus in overnutrition era

营养过剩时代的胰腺β细胞损伤与2型糖尿病的适应

• 批准号: 19209034
• 负责人: OKA Yoshitomo
• 金额: $ 31.78万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19209034/
• 关键词: インスリン分泌; 膵β細胞; 小胞体ストレス; 再生治療; 増殖

Pancreatic β cell mass contributes to the development of diabetes. We show that induction of 4E-BP1 promotes β cell survival under ER stress. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. We also found that hepatic activation of extracellular regulated kinase signaling induced pancreatic β cell proliferation through a neuronal-mediated relay of metabolic signals. Thus, inter-organ metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.

胰腺β细胞团促进糖尿病的发生。我们发现 4E-BP1 的诱导可促进 ER 应激下 β 细胞的存活。编码 4E-BP1 的 Eif4ebp1 基因被发现是转录因子 ATF4 的直接靶标。我们还发现，细胞外调节激酶信号的肝脏激活通过神经元介导的代谢信号传递诱导胰腺β细胞增殖。因此，器官间代谢中继系统可能作为糖尿病再生治疗的有价值的靶标。

项目成果

Arterial elasticity is a new parameter for evaluating atherosclerosis in subjects with visceral adiposity.

动脉弹性是评估内脏肥胖受试者动脉粥样硬化的新参数。

• 发表时间: 2009
• 作者: Yasushi Ishigaki;Ai Tokita;Hisashi Okimoto;Hideyuki Hasegawa;Makoto Kato;Yoshinori Hinokio;Hideki Katagiri;Hiroshi Kanai;Yoshitomo Oka
• 通讯作者: Yoshitomo Oka

Increased insulin demand promotes while pioglitazone prevents pancreatic beta cell apoptosis in Wfs1 knockout mice

• DOI: 10.1007/s00125-009-1270-6
• 发表时间: 2009-04-01
• 期刊: DIABETOLOGIA
• 影响因子: 8.2
• 作者: Akiyama, M.;Hatanaka, M.;Tanizawa, Y.
• 通讯作者: Tanizawa, Y.

翻訳抑制因子4E-BP1の欠損は、小胞体ストレスによる細胞障害を悪化させる

翻译抑制因子 4E-BP1 的缺乏会加剧内质网应激诱导的细胞损伤

• 发表时间: 2007
• 作者: 長野真澄;山下年晴;濱田洋美;大根田絹子;木村健一;吉川裕之;大根田修;山口賢;長野真澄;山口賢
• 通讯作者: 山口賢

ATF4-mediated induction of 4E-BP1 contributes to pancreatic β cell survival under endoplasmic reticulum stress

• DOI: 10.1016/j.cmet.2008.01.008
• 发表时间: 2008-03-01
• 期刊: CELL METABOLISM
• 影响因子: 29
• 作者: Yamaguchi, Suguru;Ishihara, Hisamitsu;Oka, Yoshitomo
• 通讯作者: Oka, Yoshitomo

Efficient and controlled gene expression in mouse pancreatic islets by arterial delivery of tetracycline-inducible adenoviral vectors

• DOI: 10.1677/jme.1.02189
• 发表时间: 2007-02-01
• 期刊: JOURNAL OF MOLECULAR ENDOCRINOLOGY
• 影响因子: 3.5
• 作者: Takahashi, Rui;Ishihara, Hisamitsu;Oka, Yoshitomo
• 通讯作者: Oka, Yoshitomo