Development of a noninvasive method for beta cell mass measurement using a nuclear magnetic resonance

• Project/Area Number: 25670258
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Kyoto University
• Principal Investigator: INAGAKI Nobuya 京都大学, 医学(系)研究科(研究院), 教授 (30241954)
• Co-Investigator(Kenkyū-buntansha): MATSUDA Tetsuya 京都大学, 大学院医学研究科, 教授 (00209561) ; TOYODA Kentaro 京都大学, 医学部附属病院, 講師 (00447971) ; KIMURA Hiroyuki 京都薬科大学, 薬学部, 准教授 (50437240)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 膵島イメージング / 19F-MRI / 膵β細胞 / インスリン分泌 / インクレチン / ＧＩＰ / Ｋ細胞 / イメージング / 糖尿病学 / Ｆ－ＭＲＩ

Outline of Final Research Achievements

We used an exendin(9-39), which bind to GLP-1 receptor specifically, as a basic frame of probe. As a results of probe characteristic analysis, we could show a specific binding against GLP-1 receptor. However, 19F peak derived from probe could not be detected on islets cells and MIN6 cells. Therefore, we synthesized a new probe used an exendin4. We analyzed the new probe using same methods. In phantom experiment of the probe using 19F-MRS, two peaks were detected. We identified a peak derived from probe with 19F because we could show that a one of the peaks was derived from TFA. However, we could not detect a peak of probe on islets and INS-1cells due to insufficiency number of 19F molecules. Though we could not establish a MR imaging probe in this period, we plane a new probe to establish the probe.

Research Products

• [Journal Article] 内科医から見た先制医療 糖尿病の先制医療 (2015)
  • Author(s): 稲垣暢也、藤田直尚、木村寛之、浜松圭太、佐野紘平、平井光春、村上淳、佐治英郎、藤本裕之
  • Journal Title: 日本内科学会雑誌 Volume: 104 Pages: 1803-1807
• [Journal Article] 膵β細胞定量―糖尿病の先制医療のために (2015)
  • Author(s): 藤田直尚、藤本裕之、稲垣暢也
  • Journal Title: 実験医学 Volume: Vol.33 No.7 Pages: 144-150
• [Journal Article] Fatty acid binding protein 5 (FABP5) regulates diet-induced obesity (DIO) via GIP secretion from enteroendocrine K-cells in response to fat ingestion. (2015)
  • Author(s): Shibue, K., Yamane, S., Harada, N., Hamasaki, A., Suzuki, K., Joo, E., Iwasaki, K., Nasteska, D., Harada, T., Hayashi, Y., Adachi, Y., Owada, Y., Takayanagi, R. and Inagaki, N.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 308 Issue: 7 Pages: 583-591
  • DOI: 10.1152/ajpendo.00543.2014
  • Peer Reviewed / Open Access
• [Journal Article] Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K-cells of upper small intestine and has a critical role in GIP secretion after fat ingestion. (2015)
  • Author(s): Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Joo E, Nasteska D, Shibue K, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N.
  • Journal Title: Endocrinology Volume: 156 Issue: 3 Pages: 837-837
  • DOI: 10.1210/en.2014-1653
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 膵β細胞定量－糖尿病の先制医療のために (2015)
  • Author(s): 藤田直尚、藤本裕之、稲垣暢也
  • Journal Title: 実験医学 Volume: 33(7) Pages: 1150-1156
• [Journal Article] Synthesis and evaluation of 18F-labeled mitiglinide derivatives as positron emission tomography tracers for β-cell imaging. (2014)
  • Author(s): H Kimura, H Matsuda H Fujimoto, K Arimitsu, K Toyoda, E Mukai, H Nakamura, Y Ogawa, M Takagi, Mo Ono, N Inagaki, H Saji.
  • Journal Title: Bioorganic & Medicinal Chemistry Volume: 22 Issue: 13 Pages: 3270-3278
  • DOI: 10.1016/j.bmc.2014.04.059
  • NAID: 120005456028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 膵β細胞イメージングの現状 (2014)
  • Author(s): 豊田健太郎、稲垣暢也
  • Journal Title: Annual Review 2014 糖尿病・代謝・内分泌 Volume: 1 Pages: 68-76
• [Journal Article] SYR-472, a novel once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor, in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. (2014)
  • Author(s): Inagaki, N., Onouchi, H., Sano, H., Funao, N., Kuroda, S., Kaku, K.
  • Journal Title: Lancet Diabtes Endocrinology Volume: 2 Issue: 2 Pages: 125-132
  • DOI: 10.1016/s2213-8587(13)70149-9
  • Peer Reviewed
• [Journal Article] Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high fat diet condition. (2014)
  • Author(s): Nasteska D, Harada N, Suzuki K, Yamane S, Hamasaki A, Joo E, Iwasaki K, Shibue K, Harada T, Inagaki N.
  • Journal Title: Diabetes Volume: 2014 Feb 28
  • NAID: 120005458283
  • Peer Reviewed
• [Journal Article] Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, 12-week study. (2013)
  • Author(s): Inagaki N, Kondo K, Yoshinari T, Maruyama N, Susuta Y, Kuki H.
  • Journal Title: Diabetes Obes.Metab. Volume: 15 Issue: 12 Pages: 1136-1145
  • DOI: 10.1111/dom.12149
  • Peer Reviewed
• [Journal Article] Reduction of reactive oxygen species ameliorates metabolism-secretion coupling in islets of diabetic GK rats by suppressing lactate overproduction (2013)
  • Author(s): Sasaki M, Fujimoto S, Sato Y, Nishi Y, Mukai E, Yamano G, Sato H, Tahara Y, Ogura K, Nagashima K, Inagaki N
  • Journal Title: Diabetes Volume: 62 Issue: 6 Pages: 1996-2003
  • DOI: 10.2337/db12-0903
  • Peer Reviewed
• [Presentation] インジウム標識Exendinプローブを用いた膵β細胞量定量の試み (2016)
  • Author(s): 藤田直尚、藤本裕之、浜松圭太、木村寛之、豊田健太郎、佐治英郎、稲垣暢也
  • Organizer: 第３０回糖尿病・肥満動物学会
  • Place of Presentation: 大宮ソニックシティ（埼玉）
  • Year and Date: 2016-03-11
• [Presentation] Non-Invasive Pancreatic Beta-Cell Imaging Using Radiolabeled Exendin Probe (2015)
  • Author(s): N.Inagaki, H. Fujimoto, H. Kimura, K. Hamamatsu, N. Fujita, and H. Saji
  • Organizer: KEY STONE SYMPOSIA”Diabetes:New Insights into Molecular Mechanisms and Therapeutic Strategies”
  • Place of Presentation: ウエスティン都ホテル（京都）
  • Year and Date: 2015-10-25
• [Presentation] 糖尿病の先制医療 (2015)
  • Author(s): 稲垣暢也、藤田直尚、木村寛之、浜松圭太、佐野紘平、平井光春、村上淳、佐治英郎、藤本裕之
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: みやこめっせ（京都）
  • Year and Date: 2015-04-10
• [Presentation] 膵β細胞特異的プローブを用いた移植膵島可視化の試み (2015)
  • Author(s): 藤田直尚、藤本裕之、木村寛之、浜松圭太、神戸香織、豊田健太郎、佐治英郎、稲垣暢也
  • Organizer: 第42回膵・膵島移植研究会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2015-03-07
• [Presentation] Ｎｏｎｉｎｖａｓｉｖｅ， ｉｎ ｖｉｖｏ ｉｍａｇｉｎｇ ｏｆ ｐａｎｃｒｅａｔｉｃ ｂ－ｃｅｌｌｓ (2014)
  • Author(s): Nobuya Inagaki，Hiroyuki Kimura, Hideo Saji, Kentaro Toyoda
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-24
• [Presentation] 膵β細胞の分子イメージングを目的とした GLP-1 受容体標的 111In 標識 Exendin-4誘導体の開発
  • Author(s): 神戸香織、木村寛之、松田洋和、小川祐、豊田健太郎、藤本裕之、小野正博、稲垣暢也、佐治英郎.
  • Organizer: 第23回金属の関与する生体関連反応シンポジウム
  • Place of Presentation: 東京
• [Presentation] 非侵襲的画像診断法を用いた糖尿病モデル動物の膵β細胞量の解析
  • Author(s): 藤本裕之、豊田健太郎、木村寛之、小川祐、庄暁桐、平井光春、松田洋和、佐治英郎、稲垣暢也．
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] 膵β細胞のイメージングを目的としたGLP-1受容体標的68Ga標識Exendin(9-39)誘導体の開発
  • Author(s): 神戸香織, 木村寛之, 松田洋和, 小川祐, 豊田健太郎, 藤本裕之, 小野正博, 稲垣暢也, 佐治英郎.
  • Organizer: 第53回日本核医学会学術集会
  • Place of Presentation: 福岡
• [Presentation] 膵β細胞イメージング : Up to Date
  • Author(s): 豊田健太郎、稲垣暢也.
  • Organizer: 第50回日本糖尿病学会近畿地方会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 膵β細胞のイメージングを目的としたGLP-1受容体結合性放射性分子プローブの開発：111In-DTPA12-Ex4の in vivo 評価
  • Author(s): 神戸香織, 木村寛之, 松田洋和, 小川祐, 豊田健太郎, 藤本裕之, 小野正博, 稲垣暢也, 佐治英郎
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本