Development of diet therapy aiming at extending healthy life expectancy based on GIP signal suppression

• Project/Area Number: 18H03171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: 株式会社関西メディカルネット(関西電力医学研究所) (2020); Akita University (2018-2019)
• Principal Investigator: Yamada Yuichiro 株式会社関西メディカルネット(関西電力医学研究所), 糖尿病研究センター, センター長 (60283610)
• Co-Investigator(Kenkyū-buntansha): 佐藤 雄大 秋田大学, 医学系研究科, 助教 (40709127) ; 桑田 仁司 株式会社関西メディカルネット(関西電力医学研究所), 糖尿病研究センター先端糖尿病研究部, 部長 (80771469)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: インクレチン / GLP-1 / GIP / 加齢 / 生活習慣病 / 老化 / 消化管ホルモン / 病態栄養学 / 糖代謝

Outline of Final Research Achievements

Incretin is a gastrointestinal factor that promotes insulin secretion after diet ingestion, and GIP and GLP-1 are main members of incretin. Blocking the GIP signal not only prolongs lifespan, but also increases activity and muscle mass. On the contrary, it was shown that enhancing the GLP-1 signal improved pulmonary influenza virus infection. Thus, it was clarified that a diet that suppresses GIP signal and activates GLP-1 signal is important for extending healthy life expectancy.

Academic Significance and Societal Importance of the Research Achievements

消化管は外界と生体の接点であり、外界から受けた刺激をもとに生体へと情報を発信する。食事は単に消化管を通過して必要な栄養素を吸収されるだけではないことが、消化管ホルモンの研究や腸管免疫の研究などからわかってきた。今回の研究は、二つのインクレチンが機能分担しており、一方を減少させ、もう一方を増加させることで健康寿命延伸に繋がる可能性があり、このような栄養療法の開発の重要性を示す研究である。

Research Products

• [Journal Article] Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms (2021)
  • Author(s): Kato Shunsuke、Sato Takehiro、Fujita Hiroki、Kawatani Masahiro、Yamada Yuichiro
  • Journal Title: Scientific Reports Volume: 11 Issue: 1
  • DOI: 10.1038/s41598-021-88612-x
  • Peer Reviewed / Open Access
• [Journal Article] GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice (2020)
  • Author(s): Sato T, Shimizu T, Fujita H, Imai Y, Drucker DJ, Seino Y, Yamada Y
  • Journal Title: Endocrinology Volume: 161(12) Issue: 12
  • DOI: 10.1210/endocr/bqaa201
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Magnitude of slowing gastric emptying by glucagon‐like peptide‐1 receptor agonists determines the amelioration of postprandial glucose excursion in Japanese patients with type?2 diabetes (2019)
  • Author(s): Suganuma Yumi、Shimizu Tatsunori、Sato Takehiro、Morii Tsukasa、Fujita Hiroki、Harada Sassa Mariko、Yamada Yuichiro
  • Journal Title: Journal of Diabetes Investigation Volume: 11 Issue: 2 Pages: 389-399
  • DOI: 10.1111/jdi.13115
  • NAID: 120007169375
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of GIP signaling extends lifespan without caloric restriction (2019)
  • Author(s): Hoizumi Manabu、Sato Takehiro、Shimizu Tatsunori、Kato Shunsuke、Tsukiyama Katsushi、Narita Takuma、Fujita Hiroki、Morii Tsukasa、Sassa Mariko Harada、Seino Yutaka、Yamada Yuichiro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 513 Issue: 4 Pages: 974-982
  • DOI: 10.1016/j.bbrc.2019.04.036
  • Peer Reviewed
• [Presentation] Rice cracker made from resistant starch-containing rice ameliorate post-prandial hyperglycemia (2019)
  • Author(s): Kuwata H, Fujiwara Y, Yabe D, Watanabe T, Sasaki T, Higuchi Y, Saito Y, Arao H, Hirayama M, Goto H, Seino Y, Watanabe K, Yamada Y, Fujita N
  • Organizer: 11th Scientific Meeting of the Asian Association for the Study of Diabetes
  • Int'l Joint Research