Comparison of GLP-1-producing cells in duodenal mucosa and gastric emptying in FD patients with pancreatic enzyme abnormalities

• Project/Area Number: 19K17444
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nippon Medical School
• Principal Investigator: Hiroshi Yamawaki 日本医科大学, 医学部, 助教 (70720051)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 機能性ディスペプシア / 膵酵素異常 / 十二指腸炎 / 早期慢性膵炎 / 機能性消化管障害 / tight junction / 膵機能障害 / 心窩部痛症候群

Outline of Research at the Start

本研究課題では、膵酵素異常を伴うFD患者を対象にして、十二指腸粘膜における炎症細胞浸潤が、十二指腸粘膜内L細胞由来のGLP-1産生に影響を与えるか、また、十二指腸粘膜におけるGLP-1産生細胞、十二指腸粘膜内好酸球浸潤が、膵酵素異常を伴うFD患者の早期胃排出能と相関しているかなどを検討することにより、機能性消化管障害患者における消化管運動機能異常の病態の一端を明らかにすることを目的としている。さらに、ヒトL細胞のcell-lineを用いて検討することで、FD患者の病態に深く関与している早期胃排出能に関与する十二指腸粘膜内GLP-1産生細胞のシグナル伝達を明らかにすることで、FD患者の治療の端緒とすることを目標としている。

Outline of Final Research Achievements

We attempted to compare early gastric emptying, which is characteristic in patients with functional dyspepsia (FD), with duodenal mucosal inflammation and GLP-1-producing cell expression. Although no significant relationship has been found at present, we were able to clarify the relationship between anxiety and pancreatic exocrine dysfunction in FD patients with pancreatic enzyme abnormalities by collecting duodenal specimens from FD patients.
Using a new acid secretion inhibitor, vonoprazan, we compared activated eosinophils in the duodenal mucosa before and after treatment with FD patients.
We strongly expect that the study of inflammation and gastrointestinal hormones in the duodenum in FD will elucidate the pathogenesis of FD. Further studies are needed.

Academic Significance and Societal Importance of the Research Achievements

機能性ディスペプシア（FD）患者において特徴的である早期胃排出能と十二指腸粘膜内炎症細胞浸潤、GLP-1産生細胞の発現量との比較検討を試みた。その過程で、膵酵素異常を有するFD患者における心理的要素と外分泌膵機能の関連性を明らかにすることができた。また、膵酵素異常を伴うFD患者における脂肪摂取後の臨床的特徴に関して国際間の比較することができた。FDの病態解明の一助を担い、臨床的特徴に関しては新たな知見を加えることができたと確信している。

Research Products

• [Journal Article] Comparison of clinical characteristics, eating behaviors, and clinical symptoms following fat intake in functional dyspepsia with functional dyspepsia with pancreatic enzyme abnormalities between Singapore and Japan (2022)
  • Author(s): Futagami Seiji、Kessoku Takaomi、Kasai Yuki、Higurashi Takuma、Nakajima Atsushi、Agawa Shuhei、Yamawaki Hiroshi、Habiro Mayu、Ueki Nobue、Sanada Iori、Yamamoto Mariko、Watanabe Yoshiyuki、Yamato Hiroshi、Yamamoto Takatsugu、Takasaki Yusuke、Ito Koichi、Hojo Mariko、Isayama Hiroyuki、Siah Kewin Tien Ho、Gwee Kok‐Ann
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 8 Pages: 1525-1533
  • DOI: 10.1111/jgh.15874
  • Peer Reviewed / Open Access
• [Journal Article] State of anxiety may be associated with exocrine pancreatic insufficiency in functional dyspepsia patients with pancreatic enzyme abnormalities (2022)
  • Author(s): Agawa Shuhei、Futagami Seiji、Yamawaki Hiroshi、Gudis Katya、Higuchi Kazutoshi、Kaneko Keiko、Habiro Mayu、Kodaka Yasuhiro、Ueki Nobue、Watanabe Yoshiyuki、Motoda Norio、Ohashi Ryuji、Iwakiri Katsuhiko
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 70 Issue: 2 Pages: 175-181
  • DOI: 10.3164/jcbn.21-67
  • NAID: 130008165950
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Early chronic pancreatitis -the strategy and problems of its diagnosis and treatment- (2021)
  • Author(s): 二神 生爾、阿川 周平、山脇 博士
  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 118 Issue: 12 Pages: 1098-1106
  • DOI: 10.11405/nisshoshi.118.1098
  • NAID: 130008127623
  • ISSN: 0446-6586, 1349-7693
  • Year and Date: 2021-12-10
  • Peer Reviewed / Open Access
• [Journal Article] Impact of clinical characteristics of colonic diverticular bleeding in extremely elderly patients treated with direct oral anti-coagulant drugs: a retrospective multi-center study (2021)
  • Author(s): Kirita Kumiko、Kodaka Yasuhiro、Shibata Yoshiaki、Ueki Nobue、Agawa Shuhei、Yamawaki Hiroshi、Niikura Ryota、Yamamichi Nobutake、Izumi Kentaro、Hojo Mariko、Maruyama Kyohei、Yamamoto Takatsugu、Gudis Katya、Watanabe Masanori、Kaise Mitsuru、Iwakiri Katsuhiko、Futagami Seiji
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 69 Issue: 2 Pages: 222-228
  • DOI: 10.3164/jcbn.20-140
  • NAID: 130008082419
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up (2021)
  • Author(s): Higuchi Kazutoshi、Futagami Seiji、Yamawaki Hiroshi、Murakami Makoto、Kirita Kumiko、Agawa Shuhei、Ikeda Go、Noda Hiroto、Kodaka Yasuhiro、Ueki Nobue、Kaneko Keiko、Gudis Katya、Ohashi Ryuji、Iwakiri Katsuhiko
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 68 Issue: 1 Pages: 86-94
  • DOI: 10.3164/jcbn.19-130
  • NAID: 130007965287
  • ISSN: 0912-0009, 1880-5086
• [Journal Article] Comparison of Functional Dyspepsia and Early Chronic Pancreatitis (2020)
  • Author(s): Futagami Seiji、Yamawaki Hiroshi、Agawa Shuhei、Ikeda Go、Noda Hiroto、Kirita Kumiko、Higuchi Kazutoshi、Gudis Katya、Murakami Makoto、Kodaka Yasuhiro、Ueki Nobue、Iwakiri Katsuhiko
  • Journal Title: Journal of Nippon Medical School Volume: 87 Issue: 1 Pages: 2-6
  • DOI: 10.1272/jnms.JNMS.2020_87-101
  • NAID: 130007807515
  • ISSN: 1345-4676, 1347-3409
  • Year and Date: 2020-02-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines (2020)
  • Author(s): Yamawaki Hiroshi、Futagami Seiji、Sakasegawa Noriko、Murakami Makoto、Agawa Shuhei、Ikeda Go、Noda Hiroto、Kirita Kumiko、Gudis Katya、Higuchi Kazutoshi、Kodaka Yasuhiro、Ueki Nobue、Iwakiri Katsuhiko
  • Journal Title: Neurogastroenterology & Motility Volume: - Issue: 8
  • DOI: 10.1111/nmo.13813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Usefulness of 3-Dimensional Flexible Endoscopy in Esophageal Endoscopic Submucosal Dissection in an Ex Vivo Animal Model (2019)
  • Author(s): Higuchi Kazutoshi、Kaise Mitsuru、Noda Hiroto、Ikeda Go、Akimoto Teppei、Yamawaki Hiroshi、Goto Osamu、Ueki Nobue、Futagami Seiji、Iwakiri Katsuhiko
  • Journal Title: Gastroenterology Research and Practice Volume: 2019 Pages: 1-5
  • DOI: 10.1155/2019/4051956
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acylated ghrelin levels were associated with depressive status, physical quality of life, endoscopic findings based on Kyoto classification in Japan (2019)
  • Author(s): Agawa Shuhei、Futagami Seiji、Yamawaki Hiroshi、Ikeda Go、Noda Hiroto、Kirita Kumiko、Higuchi Kazutoshi、Murakami Makoto、Kodaka Yasuhiro、Ueki Nobue、Akamizu Takashi、Iwakiri Katsuhiko
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 65 Issue: 1 Pages: 65-70
  • DOI: 10.3164/jcbn.18-111
  • NAID: 130007672109
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Camostat mesilate, pancrelipase and rabeprazole combination therapy improves epigastric pain in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme (2018)
  • Author(s): Yamawaki H, Futagami S, et al.
  • Journal Title: Digestion Volume: 99 Issue: 4 Pages: 283-292
  • DOI: 10.1159/000492813
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] FD患者における十二指腸内好酸球浸潤の検討 -ボノプラザンによる抗炎症作用の解析- (2022)
  • Author(s): 山脇博士、二神生爾、岩切勝彦
  • Organizer: 第103回日本消化器内視鏡学会総会
• [Presentation] シンガポールと日本における膵酵素異常を伴う機能性ディスペプシア患者群の疫学調査 (2022)
  • Author(s): 山脇博士、二神生爾
  • Organizer: 第18回日本消化管学会総会学術集会
• [Presentation] LPS刺激Urocortin 2脳槽内投与ラットを用いた消化管炎症の解析 (2020)
  • Author(s): 山脇 博士, 二神生爾, 岩切勝彦
  • Organizer: 神経消化器病学会
• [Presentation] LPS刺激Urocortin 2脳槽内投与ラットを用いた小腸粘膜内炎症の解析-acotiamideによる小腸粘膜に対する抗炎症作用の解析- (2020)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Organizer: 第21回神経消化器病学会
• [Presentation] ～日常診療における上腹部消化管診療～機能性ディスペプシアの治療の考え方 (2020)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Organizer: 第16回日本消化管学会総会学術集会
  • Invited
• [Presentation] 難治性心窩部痛症候群に対する治療戦略 (2019)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Organizer: 第105回 日本消化器病学会総会
• [Presentation] 酸分泌抑制薬治療抵抗性の心窩部痛症候群に対する治療戦略 ～年齢を考慮して～ (2019)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Organizer: 第22回 日本高齢消化器病学会総会
• [Presentation] Camostat mesilate, pancrelipase and rabeprazole combination therapy improves epigastric pain in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme abnormalities (2019)
  • Author(s): Yamawaki H, Futagami S, Kaneko K, Agawa S, Higuchi K, Murakami M, Wakabayashi M, Sakasegawa N, Kodaka Y, Ueki N, Gudis K, Kawamoto C, Iwakiri K
  • Organizer: Digestive Disease Week 2019
  • Int'l Joint Research
• [Book] Rp.+（レシピプラス）2022年春号 Vol.21 No.2 便のトラブル110番 (2022)
  • Author(s): 三原 弘
  • Total Pages: 120
  • Publisher: 南山堂
  • ISBN: 4525922222
• [Book] 『最新ガイドラインに基づく 消化器疾患診療指針 2021-’23』 (2021)
  • Author(s): 山脇 博士、二神 生爾、岩切 勝彦
  • Total Pages: 8
  • Publisher: 総合医学社
• [Book] 臨床外科 便秘の最近の治療 (2021)
  • Author(s): 山脇 博士、二神 生爾、岩切 勝彦
  • Total Pages: 7
  • Publisher: 医学書院
• [Book] 臨床雑誌 内科127巻4号 (2021)
  • Author(s): 山脇 博士、二神 生爾、岩切 勝彦
  • Total Pages: 3
  • Publisher: 南江堂
• [Book] 消化器の臨床 (2019)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Total Pages: 6
  • Publisher: ヴァン メディカル
• [Book] 消化管症候群Ⅰ (2019)
  • Author(s): 山脇 博士、二神生爾、岩切勝彦
  • Total Pages: 7
  • Publisher: 日本臨牀
• [Remarks] 日本医科大学 消化器内科学 研究業績
  • URL: https://www.nmsgastro.jp/papers/