Re-evaluation of pathophysiology in diabetes by the receptor-mediated glucagon assay

• Project/Area Number: 15K09373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Asahikawa Medical College
• Principal Investigator: Fujita Yukihiro 旭川医科大学, 医学部, 客員助教 (20451461)
• Research Collaborator: YANAGIMACHI Tsuyoshi ; TAKEDA Yasutaka ; HONJO Jun
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グルカゴン / 膵島 / 測定法

Outline of Final Research Achievements

We established novel methods to measure glucagon, GIP and GLP-1 beaded on cell-based receptor-mediated assays. We strongly speculate that these assays can reflect to physiological actions of those hormones through studies in vitro and in vivo, measuring samples during meal tolerance tests from non-dialect and diabetic subjects.
Furthermore, we established the method for selective collection of proglucagon-positive cells and identified glucagon expression in the gastrointestinal tract other than the pancreas.

Academic Significance and Societal Importance of the Research Achievements

本研究においてグルカゴン受容体結合活性に基づき、より生理的なグルカゴン作用を反映するグルカゴン測定系を樹立すること、その測定系を用いて血液や細胞・組織抽出物などを測定すること、さらに既存のイムノアッセイ法と比較検討することは、基礎研究のみならず糖尿病の病態を臨床的に再確認する上で必須であり、かつ学術的に重要で、糖尿病治療へ新たなアプローチへ応用できると確信している。

Research Products

• [Int'l Joint Research] University of British Columbia(Canada)
• [Int'l Joint Research]
• [Int'l Joint Research] University of British Columbia(Canada)
• [Journal Article] Dipeptidyl peptidase-4 inhibitor treatment induces a greater increase in plasma levels of bioactive GIP than GLP-1 in non-diabetic subjects. (2017)
  • Author(s): Yanagimachi T, Fujita Y, Takeda Y, Honjo J, Sakagami H, Kitsunai H, Takiyama Y, Abiko A, Makino Y, Kieffer TJ, Haneda M.
  • Journal Title: Mol Metab Volume: 6 Issue: 2 Pages: 226-231
  • DOI: 10.1016/j.molmet.2016.12.009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High glucose induces platelet-derived growth factor-C via carbohydrate response element-binding protein in glomerular mesangial cells. (2016)
  • Author(s): Kitsunai H, Makino Y, Sakagami H, Mizumoto K, Yanagimachi T, Atageldiyeva K, Takeda Y, Fujita Y, Abiko A, Takiyama Y, Haneda M.
  • Journal Title: Physiol Rep Volume: 4 Issue: 6 Pages: 1-13
  • DOI: 10.14814/phy2.12730
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] レセプター統合に基づくbioassay法による活性型インクレチン及びグルカゴン測定の有用性の検討 (2018)
  • Author(s): 柳町剛司、藤田征弘、本庄潤、竹田安孝、坂上英充、別所瞭一、滝山由美、安孫子亜津子、横山宏樹、太田嗣人、羽田勝計
  • Organizer: 第61回日本糖尿病学会年次学術集会, 東京
• [Presentation] Dipeptidy peptidase-4 inhibitor has a much great impact on bioactive glucose-dependent insulinotropic polypeptide in type 2 diabetes (2018)
  • Author(s): Tsuyoshi Yanagimachi, Yukihiro Fujita, Jun Honjo, Yasutaka Takeda, Hidemitsu Sakagami, Atsuko Abiko, Tsuguhito Ota, Hiroki Yokoyama, Masakazu Haneda
  • Organizer: 2018 Asia lslet Biology & Incretin Symposium, Seoul
  • Int'l Joint Research
• [Presentation] Dipeptidyl peptidase-4 inhibitor has a much great impact on bioactive glucose-dependent insulinotropic polypeptide in type 2 diabetes (2018)
  • Author(s): Tsuyoshi Yanagimachi, Yukihiro Fujita, Jun Honjo, Yasutaka Takeda, Hidemitsu Sakagami, Atsuko Abiko, Tsuguhito Ota, Hiroki Yokoyama, Masakazu Haneda
  • Organizer: 12th IDF-WPR Congress /10th AASD Scientific Meeting, Kuala Lumpur
  • Int'l Joint Research
• [Presentation] Dipeptidyl peptidase-4 inhibitor treatment more markedly increases bioactive GIP levels than GLP-1 in type 2 diabetes (2017)
  • Author(s): 7.Yanagimachi T, Fujita Y, Takeda Y, Honjo J, Sakagami H, Abiko A, Makino Y, Haneda H
  • Organizer: IDF Congress 2017
  • Int'l Joint Research