Development of specific ELISA for short-form GIP and elucidation of its secretion in human

• Project/Area Number: 16K19527
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Asahikawa Medical College
• Principal Investigator: Takeda Yasutaka 旭川医科大学, 大学病院, 医員 (90431402)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: GIP (1-30) / インクレチン / ELISA / 糖代謝 / 糖質代謝異常 / エネルギー

Outline of Final Research Achievements

The secretion of short-form gastric inhibitory polypeptide (GIP) (1-30) in human remains unclear. We developed an ELISA specific for GIP (1-30) and measured GIP (1-30) secretion during oral glucose tolerance test and cookie meal test in non-diabetics and type 2 diabetics. After both glucose and cookie load, GIP (1-30) blood levels increased. Interestingly, the increases of GIP (1-30) were much lower than those of GIP (1-42). Similarly to known incretins, the DPP-4 inhibitor increased blood GIP (1-30) levels.

Academic Significance and Societal Importance of the Research Achievements

本研究においてGIP (1-30)のELISA系を確立し、さらにヒトにおけるGIP (1-30)の分泌動態を世界に先駆けて明らかにした。GIP (1-30)が経口での糖の摂取や糖・蛋白質・脂質混成食の摂取により分泌が促進されること、即ち経口でのこれらの負荷がGIP (1-30)の分泌刺激となることや、GIP (1-42)とは末梢血中濃度が大きく異なること、既知のインクレチンと同様にDPP-4阻害薬によって分泌が増加することを見出した。以上の知見は、糖代謝における新たな調節因子としてのGIP (1-30)の役割の一端を明らかにするもので、糖尿病の病態や病因の解明の一助となる可能性を有する。

Research Products

• [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] Alternative form of glucose-dependent insulinotropic polypepide and its physiology. (2016)
  • Author(s): Fujita Y, Yanagimachi T, Takeda Y, Honjo J, Takiyama Y, Abiko A, Makino Y, Haneda M.
  • Journal Title: Journal of diabetes investigation Volume: Suppl 1 Issue: S1 Pages: 33-37
  • DOI: 10.1111/jdi.12445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] short-form GIPの測定系の確立とヒトにおける分泌動態の検討 (2019)
  • Author(s): 竹田 安孝
  • Organizer: 第62回日本糖尿病学会年次学術集会
• [Presentation] Secretion of the short-form gastric inhibitory polypeptide in non-diabetic and diabetic subjects (2019)
  • Author(s): Yasutaka Takeda
  • Organizer: American Diabetes Association's 79th Scientific Sessions
  • Int'l Joint Research