Development of a new therapy for diabetes mellitus through Betacellulin receptor cloning

通过 Betacellulin 受体克隆开发糖尿病新疗法

• 批准号: 17590915
• 负责人: OKADA Shuichi
• 金额: $ 2.44万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590915/
• 关键词: Regeneration; Betacelluli; EGF; 再生医学; シグナル伝達; 移植・再生医療; 糖尿病; 内科

We tried to identify the Betacellulin receptor cloning. 1. We made two columns. The one contains Betacellulin (BTC/1-80) which is full length. The other one contains Betacellulin (BTG2-76) which is enough portion to evoke pancreatic beta cell differentiation. We focused on the molecule which not binds to BTC-1-80 column but binds to BTC/24-76 column. We could obtain EGF receptor and BTC seems to bind and use EGF receptor as well as EGF. We could not find any other candidate molecule containing receptor structure. 2. We speculated that there might be difference of phosphorylated molecule between BTC and EGF stimuli. We stimulated βHC9 cells with either BTC or EGF and tyrosine-phosphorylated molecules were pulled down by the design of immunoprecipitation with phosphotyrosine antibody. The separated band on SDS-PAGE, which is just unique for BTC stimulation, was isolated and processed LC/MS analysis. Finally we obtained a molecule containing phospholipase D active site motif with EGFR phosphorylation site. We considered that this molecule is regulating cell proliferation through Ras activation pathway of PLD2/SostRas. Further investigation is planned as a next step.

我们试图确定β细胞素受体的克隆。1.我们做了两个专栏。其中一种含有全长的Betacellulin（BTC/1-80）。另一种含有β细胞素（BTG 2 -76），其是足以引起胰腺β细胞分化的部分。我们重点研究了不与BTC-1-80柱结合但与BTC/24-76柱结合的分子。我们可以获得EGF受体，BTC似乎与EGF受体结合并使用EGF。我们找不到任何其他含有受体结构的候选分子。2.我们推测BTC和EGF刺激后磷酸化的分子可能存在差异。我们用BTC或EGF刺激β HC 9细胞，通过磷酸酪氨酸抗体免疫沉淀的设计，将酪氨酸磷酸化分子拉下来。分离SDS-PAGE上的分离条带，其仅为BTC刺激所特有，并进行LC/MS分析。最终获得了一个含有磷脂酶D活性位点基序和EGFR磷酸化位点的分子。我们认为该分子通过PLD 2/SostRas的Ras活化途径调节细胞增殖。下一步计划进行进一步调查。

项目成果

Tyrosine phosphorylation of Muncl8c regulates PDGF-stimulated Glut4 translocation in 3T3L1 adipocytes

Muncl8c 的酪氨酸磷酸化调节 3T3L1 脂肪细胞中 PDGF 刺激的 Glut4 易位

• 发表时间: 2008
• 期刊: Endocrinology 149
• 作者: Umahara M;Okada S;et. Al.
• 通讯作者: et. Al.

Pioglitazone increases circulating adiponecctin levels and subsequently reduces TNF-alpha levels in Type 2 diabetic patients : a randomized study.

吡格列酮增加 2 型糖尿病患者循环脂联素水平，随后降低 TNF-α 水平：一项随机研究。

• 发表时间: 2006
• 期刊: Diabet Med. 23
• 作者: Hiroyuki Shimizu;Shhinsuke Oh-I;Takafumi Tsuchiya;Kenichi Ohtani;Shuichi Okada;Masatomo Mori
• 通讯作者: Masatomo Mori

Synip phosphorylation is required for insulin-stimUlated Glut4

胰岛素刺激的 Glut4 需要 Synip 磷酸化

• 发表时间: 2007
• 期刊: Biochem.Biophys.Res.Commun 365
• 作者: Okada S;et. al.
• 通讯作者: et. al.

Identification of nesfatin-1 as a satiety molecule in the hypothalamus

• DOI: 10.1038/nature05162
• 发表时间: 2006-10-12
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Oh-, Shinsuke, I;Shimizu, Hiroyuki;Mori, Masatomo
• 通讯作者: Mori, Masatomo

Synip Phosphorylation is required for insulin-stimulated Glut4.

Synip 磷酸化是胰岛素刺激的 Glut4 所必需的。

• 发表时间: 2007
• 期刊: Biochem. Biophys. Res. Commun. 356
• 作者: Okada S;et
• 通讯作者: et