Study on regulatory mechanisms of the expression and secretion of insulin-like peptides

• Project/Area Number: 23770071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Morphology/Structure
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OKAMOTO Naoki 独立行政法人理化学研究所, 成長シグナル研究チーム, 基礎科学特別研究員 (10577969)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: インスリン様ペプチド / インスリン産生細胞 / 成長 / ショウジョウバエ / インスリン / インスリン様成長因子（IGF） / 栄養 / 比較内分泌 / 生理・内分泌学 / 比較内分泌学 / 昆虫

Research Abstract

Regulatory mechanisms of the function of insulin-like peptides (ILPs) were analyzed by using fruit fly Drosophila melanogaster and mammalian pancreatic β cells-derived cell line. We found that the evolutionally conserved regulatory mechanism of the insulin expression by two transcriptional factors, Dachshund and Eyeless. We further characterized a novel ILPs-binding protein called secreted decoy of InR (SDR) that binds to ILPs in the circulating hemolymph and antagonizes insulin/IGF signaling during development.

Research Products

• [Journal Article] A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. (2013)
  • Author(s): Naoki Okamoto, Rinna Nakamori, Tomoka Murai, Yuki Yamauchi, Aya Masuda, Takashi Nishimura
  • Journal Title: Genes. Dev. Volume: 27 Pages: 87-97
  • Peer Reviewed
• [Journal Article] A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila (2013)
  • Author(s): Okamoto N, Nakamori R, Murai T, Yamauchi Y, Masuda A, Nishimura T
  • Journal Title: Genes Dev Volume: 27 Issue: 1 Pages: 87-97
  • DOI: 10.1101/gad.204479.112
  • Peer Reviewed
• [Journal Article] Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression. (2012)
  • Author(s): Naoki Okamoto, Yuka Nishimori, Takashi Nishimura
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 109 Pages: 2406-2411
  • Peer Reviewed
• [Journal Article] Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression (2012)
  • Author(s): Okamoto N, Nishimori Y, Nishimura T
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 7 Pages: 2406-2411
  • DOI: 10.1073/pnas.1116050109
  • Peer Reviewed
• [Journal Article] Spatiotemporal patterns of IGF-like peptide expression in the silkmoth Bombyx mori predict its pleiotropic actions. (2011)
  • Author(s): Okamoto Naoki, Yamanaka Naoki, Endo Yasuhisa, Kataoka Hiroshi, Mizoguchi Akira
  • Journal Title: General and Comparative Endocrinology Volume: 173 Issue: 1 Pages: 171-182
  • DOI: 10.1016/j.ygcen.2011.05.009
  • Peer Reviewed
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila (2013)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 2nd Psia-Pacific Drosophila Research Conference 2013
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2013-05-14
• [Presentation] ショウジョウバエ分泌型インスリン受容体は、体の成長を抑制する (2012)
  • Author(s): 岡本直樹,西村隆史
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 博多
  • Year and Date: 2012-12-12
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 日本ショウジョウバエ研究集会2012
  • Place of Presentation: 東京
  • Year and Date: 2012-10-15
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptide gene expression (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 日本ショウジョウバエ研究集会2012
  • Place of Presentation: 東京
  • Year and Date: 2012-10-14
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptides gene expression (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: New Frontiers of Metabolism Research in Biomedical Sciences
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2012-09-27
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptides gene expression (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 24th International Congress of Entomology 2012
  • Place of Presentation: Daegu, South Korea
  • Year and Date: 2012-08-24
• [Presentation] 昆虫インスリンの機能を調節するメカニズム (2012)
  • Author(s): 岡本直樹
  • Organizer: 2012 年度日本農芸化学会第1回例会シンポジウム「昆虫の行動を規定する化学
  • Place of Presentation: 東京
  • Year and Date: 2012-07-21
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 第46回 日本発生生物学会
  • Place of Presentation: 松江
  • Year and Date: 2012-05-31
• [Presentation] Regulation of the systemic growth by insulin-like peptides during Drosophila development (2012)
  • Author(s): Naoki Okamoto, Tomoka Murai, Takashi Nishimura
  • Organizer: 第45回 日本発生生物学会、第64回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-31
• [Presentation] Transcriptional regulation of Drosophila insulin-like peptides by nutrition (2012)
  • Author(s): Yuka Nishimori, Naoki Okamoto, Takashi Nishimura
  • Organizer: 第45回 日本発生生物学会、第64回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-31
• [Presentation] Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression (2012)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 第45回 日本発生生物学会、第64回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-29
• [Presentation] 昆虫と哺乳類で保存されたインスリン発現制御機構 (2012)
  • Author(s): 岡本直樹
  • Organizer: 名古屋大学GCOE セミナー アドバンス生命理学持論
  • Place of Presentation: 名古屋
  • Year and Date: 2012-01-27
• [Presentation] An Evolutionarily Conserved Function of Dachshund/DACH to Regulate Insulin Expression Together with Eyeless/PAX6 (2011)
  • Author(s): Naoki Okamoto, Yuka Nishimori, Takashi Nishimura
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-14
• [Presentation] 昆虫と哺乳類で保存されたDachshund/DACH によるインスリン様ペプチド発現制御機構 (2011)
  • Author(s): 岡本直樹,西村隆史
  • Organizer: 昆虫ワークショップ2011
  • Place of Presentation: 博多
  • Year and Date: 2011-10-13
• [Presentation] An Evolutionarily Conserved Function of Dachshund/DACH to Regulate Insulin Expression Together with Eyeless/PAX6, Exciting Biology Series - Cellular development (2011)
  • Author(s): Naoki Okamoto, Yuka Nishimori, Takashi Nishimura
  • Organizer: Biology at the interface
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2011-09-29
• [Presentation] A transgenic RNA interference screen for regulators of nutrient-dependent growth in the fruit fly Drosophila melanogaster (2011)
  • Author(s): Naoki Okamoto, Takashi Nishimura
  • Organizer: 第44回 日本発生生物学会
  • Place of Presentation: 沖縄
  • Year and Date: 2011-05-20
• [Presentation] A transgenic RNA interference screen for regulators of nutrient-dependent growth in the fruit fly Drosophila melanogaster. (2011)
  • Author(s): 岡本直樹，西村隆史
  • Organizer: 日本発生生物学会 第44回大会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県）
• [Presentation] An Evolutionarily Conserved Function of Dachshund/DACH to Regulate Insulin Expression Together with Eyeless/PAX6. (2011)
  • Author(s): 岡本直樹，西森由佳，西村隆史
  • Organizer: Exciting Biology Series - Cellular development: Biology at the interface
  • Place of Presentation: RIKEN CDB（兵庫県）
• [Presentation] 昆虫と哺乳類で保存されたDachshund／DACHによるインスリン様ペプチド発現制御機構 (2011)
  • Author(s): 岡本直樹，西村隆史
  • Organizer: 昆虫ワークショップ2011
  • Place of Presentation: ZAOセンタープラザ（山形県）
• [Presentation] An Evolutionarily Conserved Function of Dachshund/DACH to Regulate Insulin Expression Together with Eyeless/PAX6. (2011)
  • Author(s): 岡本直樹，西村隆史
  • Organizer: 第34回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression.
  • Author(s): 岡本直樹
  • Organizer: 第45 回 日本発生生物学会・第64 回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Transcriptional regulation of Drosophila insulin-like peptides by nutrition.
  • Author(s): 西森由佳
  • Organizer: 第45 回 日本発生生物学会・第64 回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Regulation of the systemic growth by insulin-like peptides during Drosophila development
  • Author(s): 西村隆史
  • Organizer: 第45 回 日本発生生物学会・第64 回 日本細胞生物学会合同大会
  • Place of Presentation: 神戸国際会議場
• [Presentation] 昆虫インスリンの機能を調節するメカニズム
  • Author(s): 岡本直樹
  • Organizer: 2012年度日本農芸化学会第1回例会シンポジウム
  • Place of Presentation: 東京大学
  • Invited
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptides gene expression.
  • Author(s): Naoki Okamoto
  • Organizer: 24th International Congress of Entomology 2012
  • Place of Presentation: Daegu, South Korea
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptide gene expression.
  • Author(s): Naoki Okamoto
  • Organizer: New Frontiers of Metabolism Research in Biomedical Sciences
  • Place of Presentation: 東京大学
• [Presentation] Regulatory mechanism of the Drosophila insulin-like peptide gene expression.
  • Author(s): 岡本直樹
  • Organizer: 日本ショウジョウバエ研究集会 2012
  • Place of Presentation: 東京慈恵会医科大学
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila.
  • Author(s): 西村隆史
  • Organizer: 日本ショウジョウバエ研究集会 2012
  • Place of Presentation: 東京慈恵会医科大学
• [Presentation] ショウジョウバエ分泌型インスリン受容体は、体の成長を抑制する
  • Author(s): 岡本直樹
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila.
  • Author(s): Naoki Okamoto
  • Organizer: 2nd Asia-Pacific Drosophila Research Conference
  • Place of Presentation: Seoul, South Korea
• [Presentation] Secreted decoy of InR antagonizes insulin signaling to restrict body growth in Drosophila.
  • Author(s): 岡本直樹
  • Organizer: 第46 回 日本発生生物学会
  • Place of Presentation: 島根県立産業交流会館（くにびきメッセ）
• [Book] むしむしコラム・おーどーこん -近くて不思議な虫の世界- : おとり受容体が体の成長を調節する (2013)
  • Author(s): 岡本直樹,西村隆史
  • Publisher: 日本応用動物昆虫学会電子広報委員会
• [Book] むしむしコラム・おーどーこん ー近くて不思議な虫の世界ー (2013)
  • Author(s): 岡本直樹
  • Total Pages: 1
  • Publisher: 日本応用動物昆虫学会電子広報委員会
• [Book] 脱皮・変態の生物学－昆虫と甲殻類のホルモン作用の謎を追う (2011)
  • Author(s): 岡本直樹，溝口明
  • Publisher: 東海大学出版
• [Remarks]
  • URL: http://www.cdb.riken.jp/gcs/
• [Remarks] ・産経新聞(夕刊)「ゼロからイチを生み出す」(2012年5月28日)本業績に関する新聞記事
• [Remarks] ・神戸新聞(朝刊)「成長制御のタンパク質ハエ体内から理研神戸発見糖尿病治療に応用も」(2013年1月3日)本業績に関する新聞記事
• [Remarks] ・読売新聞(夕刊)「成長制御するたんぱく質発見」(2013年1月15日)本業績に関する新聞記事
• [Remarks] 成長シグナル研究チーム
  • URL: http://www.cdb.riken.jp/gcs/index.html
• [Remarks] インスリンの「おとり」受容体が体の成長を調節する
  • URL: http://www.cdb.riken.jp/jp/04_news/articles/13/130109_secreteddecoy.html
• [Remarks] Treading a common path to metabolic maintenance
  • URL: http://www.rikenresearch.riken.jp/eng/research/6959.html
• [Remarks] インスリンの発現を調節する新たなメカニズム：昆虫と哺乳類で保存された仕組み
  • URL: http://www.cdb.riken.jp/jp/04_news/articles/12/120210_insulinregulation.html