Details of the Researcher

PHOTO

Takahiro Horiuchi
Section
Institute of Medical Research
Job title
Assistant Professor
Degree

  • MD PhD (Tohoku University)

e-Rad No.
70992428
Profile

I am a physician-scientist specializing in diabetes, metabolism, and endocrinology. My research focuses on understanding the physiological systems at the whole-body level that maintain metabolic homeostasis through coordinated interactions among multiple organs. I also aim to translate these findings into strategies to improve physiological function and develop novel therapeutic approaches for metabolic diseases. In particular, my research centers on hepatic glucose production, a critical source of glucose during exercise, and the inter-organ networks that regulate this process.

Research History 7

  • 2026/04 - Present
    SiRIUS Institute of Medical Research, Tohoku University　Distinguished Assistant Professor

  • 2025/11 - Present
    Tohoku University Hospital　Department of Diabetes, Metabolism and Endocrinology　Assistant Professor

  • 2023/04 - 2025/10
    Tohoku University　Department of Diabete, Metabolism and Endocrinology　Specially Appointed Researcher

  • 2018/04 - 2023/03
    Tohoku University School of Medicine　Department of Diabetes and Metabolism　graduate student

  • 2018/04 - 2019/03
    Tohoku Medical and Pharmaceutical University Hospital　Tohoku Medical and Pharmaceutical University

  • 2016/04 - 2018/03
    Sendai City Hospital　Junior Resident (Medical Intern)

  • 2010/04 - 2016/03
    Institute of Development, Aging and Cancer (IDAC), Tohoku University　Department of Molecular and Cellular Biology　Undergraduate Student

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Education 2

  • Tohoku University　Graduate School of Medicine　Department of Medical Sciences

    2018/04 - 2023/03

  • Tohoku University　Faculty of Medicine　School of Medicine

    2010/04 - 2016/03

Professional Memberships 7

  • Japan Society for the Study of Obecity (JASSO)

    2023/04 - Present

  • The Molecular Biology Society of Japan

    2023/03 - Present

  • Japan Atherosclerosis Society

    2023/03 - Present

  • The Japanese Biochemical Society

    2023/03 - Present

  • The Japan Endocrine Society

    2021/04 - Present

  • The Japanese Society of Internal Medicine

    2018/03 - Present

  • The Japan DIabetes Society

    2017/11 - Present

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Research Interests 5

  • Exercise

  • Obesity

  • Inter-organ network

  • Gluconeogenesis

  • Diabetes

Research Areas 1

  • Life sciences / Metabolism and endocrinology /

Awards 3

  1. Tohoku Diabetes Research Conference for Young Investigators (TRY) award

    2025/03　Tohoku Diabetes Research Conference for Young Investigators (TRY)　Elucidating the impact of exercise intensity-dependent substrate selection of gluconeogenesis

  2. Young Investigator Award (YIA)

    2024/05　Hepatic gluconeogensis modulates low- and high-intensity exercise capacity in a substrate-dependent manner

  3. Research Encouragement Award

    2023/12　The Study Group of Molecular Diabetology　Substrate-selective hepatic gluconeogensis modulates high- and low-intenisty exercise capacity

Papers 6

  1. Redox-dependent liver gluconeogenesis impacts different intensity exercise in mice Peer-reviewed

    Takahiro Horiuchi, Keizo Kaneko, Shinichiro Hosaka, Kenji Uno, Seitaro Tomiyama, Kei Takahashi, Maya Yamato, Akira Endo, Hiroto Sugawara, Yohei Kawana, Yoichiro Asai, Shinjiro Kodama, Junta Imai, Seiya Mizuno, Satoru Takahashi, Atsushi Takasaki, Hiraku Ono, Koutaro Yokote, Rae Maeda, Yuki Sugiura, Hideki Katagiri

    Nature Metabolism　2025/09/18

    DOI： 10.1038/s42255-025-01373-z 　

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    We demonstrated that lactate and glycerol serve as the predominant gluconeogenic substrates during high- and low-intensity exercise, respectively. Furthermore, we showed that lowering the cytosolic [NADH]/[NAD⁺] ratio in hepatocytes enhances gluconeogenesis from lactate or glycerol and markedly improves exercise capacity. These findings identify hepatic gluconeogenesis as a critical determinant of exercise performance and suggest that its modulation may represent a promising strategy to enhance exercise capacity.

  2. Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity Peer-reviewed

    Takahiro Horiuchi, Natsumi Sakata, Yoshihiro Narumi, Tomohiro Kimura, Takashi Hayashi, Keisuke Nagano, Keyue Liu, Masahiro Nishibori, Sohei Tsukita, Tetsuya Yamada, Hideki Katagiri, Ryutaro Shirakawa, Hisanori Horiuchi

    Journal of Biological Chemistry　292　(20)　8436-8446　2017/05

    Publisher: Elsevier BV

    DOI： 10.1074/jbc.m116.769380 　

    ISSN： 0021-9258

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    We identified High Mobility Group Box 1 (HMGB1) as a novel binding protein of metformin, a therapeutic agent for type 2 diabetes. HMGB1 is a nuclear protein that functions as an alarmin and promotes inflammation when released into the circulation. We demonstrated that metformin directly binds to the acidic tail located at the C-terminus of HMGB1, thereby exerting anti-inflammatory effects. Metformin has been suggested to confer cardiovascular protection, at least in part through its anti-inflammatory properties. Our findings provide the first direct mechanistic evidence explaining the anti-inflammatory action of metformin.

  3. Colonic inflammation triggers β cell proliferation during obesity development via a liver-to-pancreas interorgan mechanism. International-journal Peer-reviewed

    Haremaru Kubo, Junta Imai, Tomohito Izumi, Masato Kohata, Yohei Kawana, Akira Endo, Hiroto Sugawara, Junro Seike, Takahiro Horiuchi, Hiroshi Komamura, Toshihiro Sato, Shinichiro Hosaka, Yoichiro Asai, Shinjiro Kodama, Kei Takahashi, Keizo Kaneko, Hideki Katagiri

    JCI insight　10　(9)　2025/05/08

    DOI： 10.1172/jci.insight.183864 　

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    Under insulin-resistant conditions, such as obesity, pancreatic β cells adaptively proliferate and secrete more insulin to prevent blood glucose elevation. We previously reported hepatic ERK activation during obesity development to stimulate a neuronal relay system, consisting of afferent splanchnic nerves from the liver and efferent vagal nerves to the pancreas, thereby triggering adaptive β cell proliferation. However, the mechanism linking obesity with the interorgan system originating in hepatic ERK activation remains unclear. Herein, we clarified that colonic inflammation promotes β cell proliferation through this interorgan system from the liver to the pancreas. First, dextran sodium sulfate (DSS) treatment induced colonic inflammation and hepatic ERK activation as well as β cell proliferation, all of which were suppressed by blockades of the neuronal relay system by several approaches. In addition, treatment with anti-lymphocyte Peyer's patch adhesion molecule-1 (anti-LPAM1) antibody suppressed β cell proliferation induced by DSS treatment. Importantly, high-fat diet (HFD) feeding also elicited colonic inflammation, and its inhibition by anti-LPAM1 antibody administration suppressed hepatic ERK activation and β cell proliferation induced by HFD. Thus, colonic inflammation triggers adaptive β cell proliferation via the interorgan mechanism originating in hepatic ERK activation. The present study revealed a potentially novel role of the gastrointestinal tract in the maintenance of β cell regulation.

  4. Inter-organ insulin-leptin signal crosstalk from the liver enhances survival during food shortages Peer-reviewed

    Kei Takahashi, Tetsuya Yamada, Shinichiro Hosaka, Keizo Kaneko, Yoichiro Asai, Yuichiro Munakata, Junro Seike, Takahiro Horiuchi, Shinjiro Kodama, Tomohito Izumi, Shojiro Sawada, Kyoko Hoshikawa, Jun Inoue, Atsushi Masamune, Yoshiyuki Ueno, Junta Imai, Hideki Katagiri

    Cell Reports　42　(5)　112415-112415　2023/04

    Publisher: Elsevier BV

    DOI： 10.1016/j.celrep.2023.112415 　

    ISSN： 2211-1247

  5. Two cases with fulminant type 1 diabetes that developed long after cessation of immune checkpoint inhibitor treatment Peer-reviewed

    Satoko Hatayama, Shinjiro Kodama, Yohei Kawana, Sonoko Otake, Daiki Sato, Takahiro Horiuchi, Kei Takahashi, Keizo Kaneko, Junta Imai, Hideki Katagiri

    Journal of Diabetes Investigation　13　(8)　1458-1460　2022/04/29

    Publisher: Wiley

    DOI： 10.1111/jdi.13807 　

    ISSN： 2040-1116

    eISSN： 2040-1124

  6. Prostaglandin E2inhibits neutrophil extracellular trap formation through production of cyclic AMP Peer-reviewed

    Kyosuke Shishikura, Takahiro Horiuchi, Natsumi Sakata, Duc-Anh Trinh, Ryutaro Shirakawa, Tomohiro Kimura, Yujiro Asada, Hisanori Horiuchi

    British Journal of Pharmacology　173　(2)　319-331　2015/12/16

    Publisher: Wiley

    DOI： 10.1111/bph.13373 　

    ISSN： 0007-1188

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Misc. 1

  1. プロスタグランジンE2はサイクリックAMP産生を介してNETs形成を阻害する

    木村 朋寛, 宍倉 匡祐, 堀内 嵩弘, 坂田 菜摘, Trinh Duc-Anh, 白川 龍太郎, 堀内 久徳

    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[2T特p-06(2P1155)]　2015/12

    Publisher: (公社)日本生化学会

Books and Other Publications 3

  1. Journal of Clinical and Experimental Medicine（IGAKU NO AYUMI)

    Takahiro Horiuchi, Keizo Kaneko, Hideki Katagiri

    ISHIYAKU PUBLISHERS, INC.　2026/08/29

  2. Diabetology 2026

    Takahiro Horiuchi, Keizo Kaneko, Hideki Katagiri

    Shindan to Chiryo Sha, Inc.　2026/05/21

    ISBN: 9784787827746

  3. The Lipid 海外文献紹介 –レビューと考察– 肝臓インスリンシグナルによる糖・脂質代謝の空間的制御

    堀内 嵩弘

    メディカルレビュー社　2025/10

    ISBN: 9784779226892

Presentations 15

  1. Impact of Substrate-Selective Hepatic Gluconeogenesis on Exercise Capacity Invited

    Takahiro Horiuchi, Keizo Kaneko, Hideki Katagiri

    The 14th Annual AAA Research Meeting (Academy of Aging and Cardiovascular Diabetes Research)　2026/01/12

  2. Hepatic gluconeogenesis modulates exercise capacity through the flux of redox-dependent substrates into the liver. Invited

    Keizo Kaneko, Takahiro Horiuchi, Hideki Katagiri

    The 68th Annual Meeting of the Japan Diabetes Society　2025/05/29

  3. 運動強度に応じた基質選択的な肝糖新生の役割 Invited

    堀内 嵩弘, 金子 慶三, 穂坂 真一郎, 冨山 晴太郎, 大和 真弥, 高橋 圭, 今井 淳太, 片桐 秀樹

    第11回がんと代謝研究会　2025/05/28

  4. 運動強度に応じた基質選択的な糖新生が及ぼす影響の解明

    堀内 嵩弘, 金子 慶三, 穂坂 真一郎, 冨山 晴太郎, 大和 真弥, 高橋 圭, 今井 淳太, 片桐 秀樹

    2024年東北糖尿病若手研究会（TRY; Tohoku Diabetes Research Conference for Young Investigators 2024）　2025/03/01

  5. 肝糖新生は基質選択的に低強度および高強度走行の運動能に影響を及ぼす

    堀内 嵩弘, 金子 慶三, 穂坂真一郎, 冨山晴太郎, 高橋 圭, 大和 真弥, 今井 淳太, 片桐 秀樹

    第67回日本糖尿病学会年次学術集会　2024/05/17

  6. 基質選択的な肝糖新生の制御は低強度および高強度の運動能を変化させる

    堀内 嵩弘, 金子 慶三, 穂坂 真一郎, 冨山 晴太郎, 大和 真弥, 高橋 圭, 今井 淳太, 片桐 秀樹

    第34回 分子糖尿病学シンポジウム　2023/12/02

  7. Hepatic Gluconeogenesis Substrate-dependently Modulates Different-intensity Exercise Capacities

    Takahiro Horiuchi, Keizo Kaneko, Shinichiro Hosaka, Seitaro Tomiyama, Kei Takahashi, Junta Imai, Hideki Katagiri

    The 44th Annual Meeting of Japan Society for the Study of Obesity (JASSO 44)　2023/11/25

  8. 運動強度に応じた基質選択的な肝糖新生の役割と制御

    堀内嵩弘, 金子慶三, 片桐秀樹

    第98回日本生化学会大会　2025/11/05

  9. 減量・代謝改善手術後に新規肥満症治療薬セマ グルチドを導入した１例

    堀内 嵩弘, 高橋 圭, 金子 慶三, 今井 淳太, 片桐 秀樹

    第45回日本肥満学会　2024/10/19

  10. 良好な血糖推移の中でシックデイにより代謝性アシドーシス、急性腎障害を発症した1例

    矢浦 一磨, 菅原 裕人, 堀内 嵩弘, 久保 晴丸, 穂坂 真一郎, 浅井 洋一郎, 児玉 慎二郎, 高橋 圭, 金子 慶三, 今井 淳太, 片桐 秀樹

    第61回日本糖尿病学会東北地方会　2023/11/11

  11. ぶどう膜炎を契機に発見された緩徐進行1型糖尿病の1例

    宍戸 愛, 堀内 嵩弘, 大場 麻由, 小川 沙八佳, 穂坂 真一郎, 児玉 慎二郎, 高橋 圭, 金子 慶三, 今井 淳太, 片桐 秀樹

    第61回日本糖尿病学会東北地方会　2023/11/11

  12. 頻回の糖質摂取の中止により症状の改善を認めた反応性低血糖疑いの 1 例

    堀内嵩弘, 沼畑貴生, 小川沙八佳, 浅井洋一郎, 児玉慎二郎, 高橋, 圭, 金子慶三, 今井淳太, 片桐秀樹

    日本内科学会 第232回東北地方会　2024/06/22

  13. 5つの膵頭関連自己抗体が重複陽性だった、肥満を伴う緩徐進行1型糖尿病の一例

    堀内 嵩弘, 高橋 圭, 児玉 慎二郎, 橋本 麻美子, 穂坂 真一郎, 畑山 暁子, 金子 慶三, 今井 淳太, 片桐 秀樹

    第58回 日本糖尿病学会東北地方会　2020/11/07

  14. ピルビン酸キナーゼ欠損症に伴う鉄過剰症が発症の原因と疑われたブロンズ糖尿病の一例

    堀内 嵩弘, 児玉 慎二郎, 穂坂 真一郎, 橋本 麻美子, 土屋 暁子, 泊 秀史, 金子 慶三, 澤田 正二郎, 今井 淳太, 片桐 秀樹

    第57回 日本糖尿病学会東北地方会　2019/11/02

  15. 真菌性腹膜透析関連腹膜炎に感染性心内膜炎を合併した1剖検例

    堀内 嵩弘, 室谷 嘉一, 太田 耕平, 中山 晋吾, 中村 はな, 衣笠 哲史, 谷 淳一, 森 建文

    第215回 日本内科学会東北地方会　2018/09/22

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Research Projects 2

  1. Elucidating the Systemic Impact of Substrate-Selective Gluconeogenesis

    Takahiro Horiuhci

    Offer Organization: Japan Foundation for Applied Enzymatology

    System: The Medical Frontier Conference (TMFC) Research Grant

    2024/05 - 2029/03

  2. Elucidation of the role of hepatic gluconeogenesis in age-related decline in exercise capacity

    Offer Organization: Japan Society for the Promotion of Science (JSPS)

    System: Grants-in-Aid for Scientific Research (KAKENHI)

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2026/04 - 2028/03

Academic Activities 4

  1. Nature Communications, ECR co-reviewer

    2026/09 -

  2. Reviewer, Molecular and Cellular Biochemistry

    2026/08 -

  3. Session Chair, “Introduction to Internal Medicine for Medical Students, Residents, and Fellows 2026”

    2026/04/11 -

    Activity type: Academic society, research group, etc.

  4. Peer review activity for Nature Communications (ECR co-reviewer)

    2025/11 -

    Activity type: Peer review