Study of molecular basis of motilin and growth hormone secretagogue receptor

• Project/Area Number: 20K08333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Ehime University
• Principal Investigator: Matsuura Bunzo 愛媛大学, 医学系研究科, 寄附講座教授 (80284420)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: モチリン受容体 / グレリン受容体 / モチリン / エリスロマイシン / グレリン / 受容体脱感作 / トランスジェニックマウス / 脳－腸相関 / GRK / b-arrestin / 相互連関 / 受容体活性化機構 / 受容体脱感作機構

Outline of Research at the Start

生活習慣病や化学療法などに伴う消化管運動機能異常は重要な臨床課題の一つであり，モチリン受容体やグレリン受容体作動性物質の開発およびその臨床応用が切望されている。一方，リガンド－受容体の活性化の分子機構，脱感作機構の解明は，これら受容体作動性物質の開発，臨床応用において不可欠の研究課題であるが，不明な点が多く残存する。本研究課題は，受容体活性化機構，脱感作機構を解明するとともに，ヒトモチリン受容体トランスジェニックマウスを用いて，生活習慣病や各種薬剤，ストレス病態などにおける中枢と消化管，肝胆膵の臓器連関，消化管ホルモン相互の連関の解明と適切な治療法を確立することを目的とする。

Outline of Final Research Achievements

Motilin, erythromycin and ghrelin are important regulators of gastrointestinal motor function, mediated by the class A G protein-coupled motilin receptor (MLNR) and growth hormone secretagogue receptor (GHSR). We have clarified pre-stimulation with motilin induces desensitization of MLNR, while that with erythromycin does not. Intracellular GRK and b-arrestin are found to be involved in differences of the desensitization. We also have clarified gastric motility in anxiety model of MLNR transgenic mice is improved by MLNR agonist.

Academic Significance and Societal Importance of the Research Achievements

モチリン受容体におけるエリスロマイシン刺激では，細胞内GRK，b-arrestinの作用により脱感作が生じにくいため，種々の病態における消化管運動機能異常の改善に有用であることが確立された。

Research Products

• [Int'l Joint Research] Mayo Clinic Arizona(米国)
• [Int'l Joint Research] Mayo Clinic Arizona(米国)
• [Int'l Joint Research] Mayo Clinic Arizona(米国)
• [Journal Article] Fish and Polyunsaturated Fatty Acid Intake and Carotid Intima–Media Thickness in Japan: the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan (2023)
  • Author(s): Miyake Yoshihiro、Tanaka Keiko、Nagata Chisato、Senba Hidenori、Hasebe Yasuko、Miyata Toyohisa、Higaki Takashi、Kimura Eizen、Matsuura Bunzo、Kawamoto Ryuichi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 30 Issue: 8 Pages: 934-942
  • DOI: 10.5551/jat.63781
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2023-08-01
  • Peer Reviewed / Open Access
• [Journal Article] Fatty liver with metabolic disorder, such as metabolic dysfunction-associated fatty liver disease, indicates high risk for developing diabetes mellitus. (2022)
  • Author(s): Miyake T, Matsuura B, Furukawa S, Ishihara T, Yoshida O, Miyazaki M, Watanebe K, Shiomi A, Nakaguchi H, Yamamoto Y, Koizumi Y, Tokumoto Y, Hirooka M, Takeshita E, Kumagi T, Abe M, Ikeda Y, Iwata T, Hiasa Y
  • Journal Title: J Diabetes Investig Volume: 13 Issue: 7 Pages: 1245-1252
  • DOI: 10.1111/jdi.13772
  • Peer Reviewed / Open Access
• [Journal Article] Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis (2022)
  • Author(s): Teruki Miyake, Shinya Furukawa, Bunzo Matsuura, Osamu Yoshida, Masumi Miyazaki, Akihito Shiomi, Sayaka Kanzaki, Hironobu Nakaguchi, Kotaro Sunago, Yoshiko Nakamura, Yusuke Imai, Takao Watanabe, Yasunori Yamamoto, Yohei Koizumi, Yoshio Tokumoto, Masashi Hirooka, Teru Kumagi, Masanori Abe, Yoichi Hiasa
  • Journal Title: Biomedicines Volume: 10 Issue: 10 Pages: 2540-2540
  • DOI: 10.3390/biomedicines10102540
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of human carbonic anhydrase I suppresses colitis in a murine inflammatory bowel disease model. (2022)
  • Author(s): Tange K, Yagi S, Takeshita E, Abe M, Yamamoto Y, Tomida H, Kawamura T, Hanayama M, Matsuura B, Ikeda Y, Hiasa Y
  • Journal Title: Sci Rep Volume: 12 Issue: 1 Pages: 17983-17983
  • DOI: 10.1038/s41598-022-22455-y
  • Peer Reviewed / Open Access
• [Journal Article] Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan (2022)
  • Author(s): Kumon Hiroshi、Miyake Yoshihiro、Yoshino Yuta、Iga Jun-ichi、Tanaka Keiko、Senba Hidenori、Kimura Eizen、Higaki Takashi、Matsuura Bunzo、Kawamoto Ryuichi、Ueno Shu-ichi
  • Journal Title: Canadian Journal of Diabetes Volume: 46 Issue: 8 Pages: 829-834
  • DOI: 10.1016/j.jcjd.2022.06.004
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between hearing loss and prevalence of depressive symptoms in Japan: baseline data from the Aidai Cohort Study in Yawatahama and Uchiko (2022)
  • Author(s): Nobori Junichiro、Miyake Yoshihiro、Tanaka Keiko、Senba Hidenori、Okada Masahiro、Takagi Daiki、Teraoka Masato、Yamada Hiroyuki、Matsuura Bunzo、Hato Naohito
  • Journal Title: Archives of Gerontology and Geriatrics Volume: 102 Pages: 104735-104735
  • DOI: 10.1016/j.archger.2022.104735
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between body composition and the histology of non‐alcoholic fatty liver disease: a cross‐sectional study (2021)
  • Author(s): Miyake Teruki、Miyazaki Masumi、Yoshida Osamu、Kanzaki Sayaka、Nakaguchi Hironobu、Nakamura Yoshiko、Watanabe Takao、Yamamoto Yasunori、Koizumi Yohei、Tokumoto Yoshio、Hirooka Masashi、Furukawa Shinya、Takeshita Eiji、Kumagi Teru、Ikeda Yoshio、Abe Masanori、Toshimitsu Kumiko、Matsuura Bunzo、Hiasa Yoichi
  • Journal Title: BMC Gastroenterology Volume: 21 Issue: 1 Pages: 170-170
  • DOI: 10.1186/s12876-021-01748-y
  • Peer Reviewed / Open Access
• [Journal Article] Nonalcoholic fatty liver disease is a risk factor for glucose intolerance onset in men regardless of alanine aminotransferase status (2021)
  • Author(s): Miyake Teruki、Matsuura Bunzo、Furukawa Shinya、Yoshida Osamu、Hirooka Masashi、Kumagi Teru、Ishihara Toru、Kanzaki Sayaka、Nakaguchi Hironobu、Miyazaki Masumi、Nakamura Yoshiko、Yamamoto Yasunori、Koizumi Yohei、Tokumoto Yoshio、Takeshita Eiji、Ikeda Yoshio、Abe Masanori、Kitai Kohichiro、Hiasa Yoichi
  • Journal Title: Journal of Diabetes Investigation Volume: 12 Issue: 10 Pages: 1890-1898
  • DOI: 10.1111/jdi.13548
  • Peer Reviewed / Open Access
• [Journal Article] Education and household income and carotid intima-media thickness in Japan: baseline data from the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan (2021)
  • Author(s): Miyake Yoshihiro、Tanaka Keiko、Senba Hidenori、Hasebe Yasuko、Miyata Toyohisa、Higaki Takashi、Kimura Eizen、Matsuura Bunzo、Kawamoto Ryuichi
  • Journal Title: Environmental Health and Preventive Medicine Volume: 26 Issue: 1 Pages: 88-88
  • DOI: 10.1186/s12199-021-01011-6
  • NAID: 210000159304
  • Peer Reviewed / Open Access
• [Journal Article] Higher number of teeth is associated with decreased prevalence of hearing impairment in Japan (2021)
  • Author(s): Tanaka Keiko、Okada Masahiro、Kato Hiromasa、Utsunomiya Hisanori、Senba Hidenori、Takagi Daiki、Teraoka Masato、Yamada Hiroyuki、Matsuura Bunzo、Hato Naohito、Miyake Yoshihiro
  • Journal Title: Archives of Gerontology and Geriatrics Volume: 97 Pages: 104502-104502
  • DOI: 10.1016/j.archger.2021.104502
  • Peer Reviewed / Open Access
• [Journal Article] The mechanism of increased intestinal palmitic acid absorption and its impact on hepatic stellate cell activation in nonalcoholic steatohepatitis. (2021)
  • Author(s): Hanayama M, Yamamoto Y, Utsunomiya H, Yoshida O, Liu S, Mogi M, Matsuura B, Takeshita E, Ikeda Y, Hiasa Y
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 13380-13380
  • DOI: 10.1038/s41598-021-92790-z
  • Peer Reviewed / Open Access
• [Journal Article] アルカリフォスファターゼ(ALP) (2021)
  • Author(s): 松浦文三
  • Journal Title: Medical Practice Volume: 38 Pages: 473-473
• [Journal Article] 血中ACTH値，コルチゾール値の読み方 (2021)
  • Author(s): 松浦文三
  • Journal Title: Medical Practice Volume: 38 Pages: 799-799
• [Journal Article] Tricks and traps of ICG endoscopy for effectively applying endoscopic transsphenoidal surgery to pituitary adenoma (2020)
  • Author(s): Inoue Akihiro、Kohno Shohei、Ohnishi Takanori、Nishida Naoya、Suehiro Satoshi、Nakamura Yawara、Matsumoto Shirabe、Nishikawa Masahiro、Ozaki Saya、Shigekawa Seiji、Watanabe Hideaki、Senba Hidenori、Nakaguchi Hironobu、Taniwaki Mashio、Matsuura Bunzo、Kitazawa Riko、Kunieda Takeharu
  • Journal Title: Neurosurgical Review Volume: 9 Issue: 4 Pages: 1382-1382
  • DOI: 10.1007/s10143-020-01382-4
  • Peer Reviewed / Open Access
• [Journal Article] Advanced fibrosis of non-alcoholic steatohepatitis affects the significance of lipoprotein(a) as a cardiovascular risk factor (2020)
  • Author(s): Konishi K, Miyake T, Furukawa S, Senba H, Kanzaki S, Nakaguchi H, Yukimoto A, Nakamura Y, Watanabe T, Koizumi Y, Yoshida O, Tokumoto Y, Hirooka M, Kumagi T, Abe M, Matsuura B, Hiasa Y.
  • Journal Title: Atherosclerosis Volume: 299 Pages: 32-37
  • DOI: 10.1016/j.atherosclerosis.2020.02.026
  • Peer Reviewed
• [Journal Article] Treatment on the spleen prevents the progression of secondary sarcopenia in patients with liver cirrhosis (2020)
  • Author(s): Hirooka M, Koizumi Y, Tanaka T, Nakamura Y, Sunago K, Yukimoto A, Watanabe T, Yoshida O, Miyake T, Tokumoto Y, Matsuura B, Abe M, Hiasa Y
  • Journal Title: Hepatol Commun Volume: 4 Issue: 12 Pages: 1812-1823
  • DOI: 10.1002/hep4.1604
  • Peer Reviewed / Open Access
• [Journal Article] 愛媛県下の糖尿病性腎臓病重症化予防の取り組み (2020)
  • Author(s): 松浦文三，仙波英徳，日浅陽一
  • Journal Title: 愛媛医学 Volume: 39 Pages: 59-64
  • Peer Reviewed
• [Presentation] 若年層における運動習慣の頻度，強度，パートナーを伴う運動習慣は，機能性ディスペプシアと負の関連にある (2022)
  • Author(s): 山本安則，古川慎哉，白石佳奈，橋本悠，丹下洋和，富田英臣，竹下英次，池田宜央，松浦文三，日浅陽一
  • Organizer: 第18回日本消化管学会総会学術集会
  • Invited
• [Presentation] 腹腔鏡下スリーブ状胃切除術が有効な糖尿病例の検討 (2022)
  • Author(s): 松浦文三，三宅映己，日浅陽一
  • Organizer: 第108回日本消化器病学会総会
  • Invited
• [Presentation] 愛媛県における糖尿病性腎臓病重症化予防の取組み (2022)
  • Author(s): 松浦文三，中口博允，神崎さやか，三宅映己，古川慎哉，仙波英徳，原泰彦，稲田暢，藤堂裕彦，吉田直彦，上田晃久，新谷哲司，扇喜真紀，宮内省蔵，南尚佳，酒井武則，川本龍一，菊池良夫，武市佳己，宮岡弘明
  • Organizer: 第37回日本糖尿病合併症学会
• [Presentation] 減量/代謝改善手術を選択した超高度肥満例の特徴 (2022)
  • Author(s): 松浦文三，中口博允，神崎さやか，宮﨑万純，塩見亮人，越智拓哉，村上慶匡，三宅映己，古川慎哉，日浅陽一，古賀繁宏，吉田素平，渡部祐司
  • Organizer: 第40回日本肥満症治療学会学術集会
• [Presentation] Outcome of intensive treatment for obesity at our hospital (2021)
  • Author(s): Matsuura B, Senba H, Kanzaki S, Nakaguchi H, Miyazaki M, Watanabe K, Miyake T, Furukawa S, Hiasa Y
  • Organizer: 23rd European Congress of Endocrinology
  • Int'l Joint Research
• [Presentation] Outcome of intensive treatment for obesity at our hospital (2021)
  • Author(s): Matsuura B, Senba H, Nakaguchi H, Miyazaki M, Watanabe K, Miyake T, Furukawa S, Hiasa Y
  • Organizer: UEG Week 2021
  • Int'l Joint Research
• [Presentation] Trans-fatty acids exacerbate fat deposition in the liver and reduce fat accumulation in the visceral adipose tissue by upregulating GPAM which regulates TG release from the liver (2021)
  • Author(s): Miyake T, Yoshida O, Abe M, Miyazaki M, Nakaguchi H, Yukimoto A, Watanabe T, Koizumi Y, Tokumoto Y, Hirooka M, Matsuura B, Hiasa Y
  • Organizer: AASLD 2021
  • Int'l Joint Research
• [Presentation] ヒトモチリン受容体トランスジェニックマウスを用いてのモチリン受容体アゴニストとグレリンの作用発現に関する研究 (2021)
  • Author(s): 川村智恵，松浦文三，日浅陽一
  • Organizer: JDDW 2021
• [Presentation] A relationship between motilin and ghrelin in human motilin receptor transgenic mice (2020)
  • Author(s): A relMatsuura B, Kawamura T, Nakaguchi H, Kanzaki S, Senba H, Miyake T, Furukawa S, Hiasa Y
  • Organizer: European Congress of Endocrinology
  • Int'l Joint Research
• [Presentation] 肥満症の病態と治療 (2020)
  • Author(s): 松浦文三
  • Organizer: 日本内分泌学会四国支部学術集会
  • Invited
• [Book] 病態栄養専門医テキスト(第3版) (2021)
  • Author(s): 日本病態栄養学会編
  • Total Pages: 338
  • Publisher: 南江堂
  • ISBN: 9784524228058
• [Remarks] 愛媛大学 大学院医学系研究科 医学専攻 地域生活習慣病・内分泌学講座
  • URL: https://www.m.ehime-u.ac.jp/course/