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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591351
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagoya University
• Principal Investigator: MURATA Yoshiharu 名古屋大学, 環境医学研究所, 教授 (80174308)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Yoshitaka 名古屋大学, 環境医学研究所, 准教授 (80420363) ; TAKAGISHI Yoshiko 名古屋大学, 環境医学研究所, 助教 (50024659)
• Project Period (FY): 2011 – 2013
• Keywords: グルカゴン / 膵島 / α細胞 / 転写因子 / ARX / 膵臓

Research Abstract

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.

Research Products

• [Journal Article] Aristaless-related homeobox plays a key role in hyperplasia of the pancreas isletα-like cells in mice deficient in proglucagon-derived peptides (2013)
  • Author(s): Sai Xu, Yoshitaka Hayashi, Yoshiko Takagishi, Mariko Itoh, Yoshiharu Murata
  • Journal Title: PLoS ONE Volume: 8(5) Pages: e64415
• [Journal Article] Ectopic expression of GIP in pancreaticβcells maintains enhanced insulin secretion in mice with complete absence of proglucagon–derived peptides (2013)
  • Author(s): Ayako Fukami, Yusuke Seino, Nobuaki Ozaki, Michiyo Yamamoto, Chisato Sugiyama, Eriko Sakamoto-Miura, Tatsuhito Himeno, Yoshiharu Murata, Yutaka Seino, Yutaka Oiso, Yoshitaka Hayashi
  • Journal Title: Diabetes Volume: 62 Pages: 510-518
• [Journal Article] Fertility and pregnancy-associatedβ-cell proliferation in mice deficient in proglucagon-derived peptides (2012)
  • Author(s): Chisato Sugiyama, Michiyo Yamamoto, Tomomi Kotani, Fumitaka Kikkawa, Yoshiharu Murata, Yoshihtaka Hayashi
  • Journal Title: PLoS ONE Volume: 7 Pages: e4375
• [Journal Article] Mice lacking the calcineurin inhibitor Rcan2 have an isolated defect of osteoblast function (2012)
  • Author(s): Duncan JH Basset, John G Logan, Alan Boyde, Moira Cheung, Holly Evans, Peter Crocher, Xia-yan Sun, Sai Xu, Yoshiharu Murata, Graham R Williams
  • Journal Title: Endocrinology Volume: 153 Pages: 3537-3548
• [Journal Article] Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides (2012)
  • Author(s): Chika Watanabe, Yusuke Seino, Hiroki Miyahira, Michiyo Yamamoto, Ayako Fukami, Nobuaki, Ozaki, Yoshiko Takagishi, Jun Sato, Tsutomu Fukuwatari, Katsumi Shibata, Yutaka Oiso, Yoshiharu Murata, Yoshitaka Hayashi
  • Journal Title: Diabetes Volume: 61 Pages: 78-84
• [Presentation] Blood glucose levels and isletα-cell mass in mouse models carrying mutant Arx alleles (2012)
  • Author(s): Sai Xu,林良敬,村田善晴
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20120000
• [Presentation] Innervation and vascularization into islets of Langerhans in the presence or absence of proglucagon-derived peptides (2012)
  • Author(s): Yoshitaka Hayashi, Hiroyuki Tanaka, Noriko Sanzen, Kiyotoshi Sekiguchi, Yoshiharu Murata
  • Organizer: 15^<th> International/14^<th> European Congress of Endocrinology
  • Place of Presentation: Florence, Italy
  • Year and Date: 20120000