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A study of neuronal and hormonal mediations of insulin secretion by inretins.

Research Project

Project/Area Number 24591340
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionJichi Medical University

Principal Investigator

KAKEI Masafumi  自治医科大学, 医学部, 教授 (90214270)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsinsulin secretion / incretin / diabetes / membrane potential / インスリン分泌 / 糖尿病 / 膜電位機構 / TRPチャネル / グルコース刺激インスリン分泌 / インクレチン / イオンチャネル
Outline of Final Research Achievements

In this stduy, we clarified the mechanistic pathway for stimulation of insulin secretion by incretins that include GLP-1 and GIP. These hormones open TRPM2 channel (transient receptor potential channe) that is a class of background current channel and its openings evoke increase in membrane excitability of pancreatic beta cells and consequently potentiate insulin secretion induced by glucose. We are expecting a novel antidiabetic drugs development as a target site against this channel protein.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (19 results)

All 2015 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (7 results)

  • [Journal Article] Partial Blockade of Kv2.1 Channel Potentiates GLP-1's Insulinotropic Effects in Islets and Reduces Its Dose Required for Improving Glucose Tolerance in Type 2 Diabetic Male Mice.2015

    • Author(s)
      Sukma Rita, R., K. Dezaki, T. Kurashina, M. Kakei, and T. Yada,
    • Journal Title

      Endocrinology.

      Volume: Endocrinology. 1(1): Issue: 1 Pages: 114-123

    • DOI

      10.1210/en.2014-1728

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity.2015

    • Author(s)
      Iwasaki, Y., Y. Maejima, S. Suyama, M. Yoshida, T. Arai, K. Katsurada, P. Kumari, H. Nakabayashi, M. Kakei, and T. Yada,
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol.

      Volume: 308 Issue: 5 Pages: R360-R369

    • DOI

      10.1152/ajpregu.00344.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prediction of 90-day mortality in patients without diabetes by severe hypoglycemia: blood glucose level as a novel marker of severity of underlying disease.2015

    • Author(s)
      Tsujimoto, T., R. Yamamoto-Honda, H. Kajio, M. Kishimoto, H. Noto, R. Hachiya, A. Kimura, M. Kakei, and M. Noda,
    • Journal Title

      Acta Diabetol.

      Volume: 52 Issue: 2 Pages: 307-314

    • DOI

      10.1007/s00592-014-0640-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of cAMP-EPAC-TRPM2 activation in glucose- and incretin-induced insulin secretion2014

    • Author(s)
      Yoshida M, Dezaki K, Uchida K, Kodera S, Lam NV, Ito K, Rita RS, Yamada H, Shimomura K, Ishikawa SE, Sugawara H, Kawakami M, Tominaga M, Yada T, Kakei M
    • Journal Title

      Diabetes

      Volume: (Epub ahead of print) Issue: 10 Pages: 3394-3403

    • DOI

      10.2337/db13-1868

    • NAID

      40020531124

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of cAMP-EPAC-TRPM2 activation in glucose- and incretin-induced insulin secretion.2014

    • Author(s)
      Masashi Yoshida, Katsuya Dezaki, Kunitoshi Uchida, Shiho Kodera, Nien V. Lam, Kiyonori Ito, Rauza S. Rita, Hodaka Yamada, Kenju Shimomura, San-e Ishikawa, Hitoshi Sugawara, Masanobu Kawakami, Makoto Tominaga, Toshihiko Yada Masafumi Kakei1
    • Journal Title

      Diabetes

      Volume: in press

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vital signs, QT prolongation, and newly diagnosed cardiovascular disease during severe hypoglycemia in type 1 and type 2 diabetic patients.2014

    • Author(s)
      Tsujimoto T, Yamamoto-Honda R, Kajio H, Kishimoto M, Noto H, Hachiya R, Kimura A, Kakei M, Noda M:
    • Journal Title

      Diabetes Care

      Volume: 37 Pages: 217-225

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serotonin regulates glucose-stimulated insulin secretion from pancreatic beta cells during pregnancy2013

    • Author(s)
      Ohara-Imaizumi M, Kim H, Yoshida M, Fujiwara T, Aoyagi K, Toyofuku Y, Nakamichi Y, Nishiwaki C, Okamura T, Uchida T, Fujitani Y, Akagawa K, Kakei M, Watada H, German MS, Nagamatsu S:
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 110 Pages: 19420-19425

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Insulin Activates Vagal Afferent Neurons Including those Innervating Pancreas via Insulin Cascade and Ca2+ Influx: Its Dysfunction in IRS2-KO Mice with Hyperphagic Obesity.2013

    • Author(s)
      Iwasaki Y1, Shimomura K, Kohno D, Dezaki K, Ayush EA, Nakabayashi H, Kubota N, Kadowaki T, Kakei M, Nakata M, Yada T.
    • Journal Title

      PLoS One.

      Volume: 8

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of insulin secretion from rat pancreatic islets by dexmedetomidine and medetomidine, two sedatives frequently used in clinical settings2013

    • Author(s)
      Yamato Kodera, S., Yoshida, M., Dezaki, K., Yada, T., Murayama, T., Kawakami, M., and Kakei, M.
    • Journal Title

      Endocr J

      Volume: 60 Pages: 337-346

    • NAID

      10031170619

    • Related Report
      2012 Research-status Report
  • [Journal Article] alpha-Lipoic acid protects against arsenic trioxide-induced acute QT prolongation in anesthetized guinea pigs2013

    • Author(s)
      Kumazaki, M., Ando, H., Kakei, M., Ushijima, K., Taniguchi, Y., Yoshida, M., Yamato, S., Washino, S., Koshimizu, T.A., and Fujimura, A
    • Journal Title

      Eur J Pharmacol

      Volume: 705 Pages: 1-10

    • Related Report
      2012 Research-status Report
  • [Journal Article] Pancreatic polypeptide and peptide YY3-36 induce Ca2+ signaling in nodose ganglion neurons2013

    • Author(s)
      Iwasaki, Y., Kakei, M., Nakabayashi, H., Ayush, E.A., Hirano-Kodaira, M., Maejima, Y., and Yada, T.
    • Journal Title

      Neuropeptides

      Volume: 47 Pages: 19-23

    • Related Report
      2012 Research-status Report
  • [Journal Article] Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet beta-cells2012

    • Author(s)
      Damdindorj, B., Dezaki, K., Kurashina, T., Sone, H., Rita, R., Kakei, M., and Yada, T.
    • Journal Title

      FEBS Lett

      Volume: 586 Pages: 2555-2562

    • Related Report
      2012 Research-status Report
  • [Presentation] 膵β細胞Trpm2チャネルはインクレチンホルモン・グルコース代謝依存性に開港し、インスリン分泌を刺激する2014

    • Author(s)
      吉田昌史、出崎克也、中田正範、山田穂高、石川三衛、矢田俊彦、川上正舒、加計正文
    • Organizer
      第57回日本糖尿病学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] GRP40/FFR1を介する新規インスリン分泌メカニズム2014

    • Author(s)
      山田穂高、吉田昌史、伊藤聖学、川上正舒、矢田俊彦、石川三衛、加計正文
    • Organizer
      第57回日本糖尿病学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-22 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膵β細胞Trpm2チャネルは,インクレチンホルモン・グルコース代謝依存性に開口し,インスリン分泌を 促進する2014

    • Author(s)
      吉田昌史
    • Organizer
      日本糖尿病学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] Serotonin Regulates Glucose Stimulated Insulin Secretion from Pancreatic β-Cells during Pregnancy2013

    • Author(s)
      MICA OHARA-IMAIZUMI, HAIL KIM, MASASHI YOSHIDA, YUKIKO TOYOFUKU, TADASHI OKAMURA, TOYOYOSHI UCHIDA, YOSHIO FUJITANI, MASAFUMI KAKEI, HIROTAKA WATADA, MICHAEL S. GERMAN, SHINYA NAGAMATSU,
    • Organizer
      73rd Scientific Session of American Diabetes Association
    • Place of Presentation
      Chicago
    • Related Report
      2013 Research-status Report
  • [Presentation] Activation of Trpm2 Channel by Glucose Metabolism and GLP-1 in Pancreatic Beta-Cell2013

    • Author(s)
      MASASHI YOSHIDA, SHIHO YAMATO, KATSUYA DEZAKI, MASANOBU KAWAKAMI, TOSHIHIKO YADA, MASAFUMI KAKEI
    • Organizer
      73rd Scientific Session of American Diabetes Association
    • Place of Presentation
      Chicago
    • Related Report
      2013 Research-status Report
  • [Presentation] 膵β細胞グルコース刺激活動電位形成持のCa2+依存性Kv2.1チャネルの役割2012

    • Author(s)
      吉田昌史、中田正範、大和志保、出崎克也、石川三衛、川上正舒、矢田俊彦、加計正文
    • Organizer
      第55回日本糖尿病学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 妊娠期膵β細胞でのセロトニンによるインスリン分泌亢進機構2012

    • Author(s)
      今泉美佳、吉田昌史、豊福優希子、青柳共太、中道洋子、西脇知世乃、加計正文、綿田裕孝、永松信哉
    • Organizer
      第55回日本糖尿病学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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