Role of the transcription factor, ARX, on the pancreatic islets and intesitnal endocrine cells

转录因子 ARX 对胰岛和肠内分泌细胞的作用

• 批准号: 23591351
• 负责人: MURATA Yoshiharu
• 金额: $ 3.24万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591351/
• 关键词: グルカゴン; 膵島; α細胞; 転写因子; ARX; 膵臓; ランゲルハンス島; 過形成

A transcription factor, aristaless-related homeobox (ARX), is known to play a pivotal role in the development of pancreatic islet cells. However, its precise mechanism remains to be clarified. We recently found that a marked hyperplasia was associated with increased expression of ARX in the pancreatic islet in mice deficient in glucagon gene-derived peptides. In this study, we sought to elucidate the role of ARX in the hyperplasia of alpha cells through analyses of two Arx mutant alleles that have different levels of impairment of their function. The increase in islet size and number of alpha-like cells were reduced in those mutant mice, indicating that the alpha cell hyperplasia induced by the inactivation of glucagon gene is reduced by introduction of an Arx mutation. In addition, the reduction was correlated with severity of disrupted ARX function, showing that the function of ARX is one of the key modifiers for the proliferation of pancreatic alpha cells.

已知转录因子（ARX）在胰岛细胞的发展中起着关键作用。但是，其确切的机制仍有待澄清。我们最近发现，明显的增生与缺乏胰高血糖素基因衍生肽的小鼠胰岛中ARX的表达增加有关。在这项研究中，我们试图通过分析两个具有不同水平的功能障碍的ARX突变等位基因来阐明ARX在α细胞增生中的作用。在那些突变小鼠中，胰岛大小的增加和α样细胞的数量减少，表明通过引入ARX突变降低了胰高血糖素基因诱导的α细胞增生。此外，还原与ARX函数中断的严重程度相关，表明ARX的功能是胰腺α细胞增殖的关键修饰符之一。

项目成果

Ectopic expression of GIP in pancreatic β-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides.

• DOI: 10.2337/db12-0294
• 发表时间: 2013-02
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Fukami A;Seino Y;Ozaki N;Yamamoto M;Sugiyama C;Sakamoto-Miura E;Himeno T;Takagishi Y;Tsunekawa S;Ali S;Drucker DJ;Murata Y;Seino Y;Oiso Y;Hayashi Y
• 通讯作者: Hayashi Y

プログルカゴン由来ペプチドの欠損が高脂肪食による糖代謝異常に及ぼす影響

胰高血糖素原肽缺乏对高脂饮食所致糖代谢异常的影响

• 发表时间: 2013
• 作者: 3.木下佳大;尾崎信暁;高木祐輔;清野祐介;村田善晴;押田芳治;林 良敬
• 通讯作者: 林 良敬

Mice Lacking the Calcineurin Inhibitor Rcan2 Have an Isolated Defect of Osteoblast Function

• DOI: 10.1210/en.2011-1814
• 发表时间: 2012-07-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Bassett, J. H. Duncan;Logan, John G.;Williams, Graham R.
• 通讯作者: Williams, Graham R.

Fertility and pregnancy-associatedβ-cell proliferation in mice deficient in proglucagon-derived peptides

缺乏胰高血糖素原衍生肽的小鼠的生育力和妊娠相关的β细胞增殖

• 发表时间: 2012
• 期刊: PLoS ONE
• 影响因子: 3.7
• 作者: Chisato Sugiyama;Michiyo Yamamoto;Tomomi Kotani;Fumitaka Kikkawa;Yoshiharu Murata;Yoshihtaka Hayashi
• 通讯作者: Yoshihtaka Hayashi