Development of the novel diagnostic method for quantification ofpancreatic beta-cell mass by magnetic resonance imaging
Project/Area Number |
22390185
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Kyoto University |
Principal Investigator |
INAGAKI Nobuya 京都大学, 医学(系)研究科, 教授 (30241954)
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Co-Investigator(Kenkyū-buntansha) |
TOYODA Kentaro 京都大学, 医学(系)研究科, 講師 (00447971)
MATSUDA Tetsuya 京都大学, 情報学研究科, 教授 (00209561)
TOGASHI Kaori 京都大学, 医学(系)研究科, 教授 (90135484)
木村 寛之 京都大学, 薬学研究科, 助教 (50437240)
上田 真史 京都大学, 医学(系)研究科, 助教 (40381967)
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Project Period (FY) |
2010 – 2012
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Project Status |
Completed (Fiscal Year 2012)
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Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2010: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | エネルギー / 糖質代謝異常 / イメージング / 糖尿病 / 可視化 / 糖代謝異常 |
Research Abstract |
The volume of pancreatic β-cells is known to decrease during development and progression of diabetes. The aim of this study is to develop the technique of measurement of β -cell volume in vivo by using magnetic resonance imaging (MRI). We first evaluated whether pancreatic islets were detected by various analytical parameters of MRI with or without the common enhancerssuch as Gd-solution or not, however, they were not imaged. Second, we tried to perform MRI by using newly developed probe. We synthesized the probe by adding the fluorine to one of the ligands ofglucagon-like peptide-1 receptor (GLP-1R), exendin(9-39), which is specifically expressed on pancreatic β-cells. However, contrary to our preliminary experiment, no signals were detected at all. Same analysis using INS-1 cell line showed similar poor results. The reason of this poor signal was suggested to be due to the extremely low affinity of our fluorine-labeled exendin(9-39) to GLP-1R compared to intact exendins. Therefore, we synthesized new probe that fluorine was added to exendin-4, another GLP-1R ligand, and it showed similar binding affinity to intact exendins. We are now planning to perform MRI analysis by using this new probe.
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Sasaki, M., Fujimoto, S., Inagaki, N.2013
Author(s)
Sasaki, M., Fujimoto, S., Inagaki, N.
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Journal Title
Diabetes
Volume: 62
Pages: 1996-2003
Related Report
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[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.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.2013
Author(s)
Suzuki K, Harada N, Yamane S, Nakamura Y, Sasaki K, Nasteska D, Joo E, Shibue K, Harada T, Hamasaki A, Toyoda K, Nagashima K, Inagaki N.
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Journal Title
J Biol Chem.
Volume: 288
Issue: 3
Pages: 1929-1938
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Systems analysis of GLP-1 receptor signaling in pancreatic ・-cells.2011
Author(s)
Takeda, Y., Amano, A., Noma, A., Nakamura, Y., Fujimoto, S., and Inagaki, N
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Journal Title
Am. J. Physiol.-Cell Physiol.
Volume: 301
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[Journal Article] The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice2011
Author(s)
Ogawa E, Hosokawa M, Harada N, Yamane S, Hamasaki A, Toyoda K, Fujimoto S, Fujita Y, Fukuda K, Tsukiyama K, Yamada Y, Seino Y, Inagaki N.
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Journal Title
Biochem.Biophys.Res.Commun.
Volume: 404
Pages: 115-120
NAID
Related Report
Peer Reviewed
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[Journal Article] Exendin-4 protects pancreatic beta cells from the cytotoxic effect of rapamycin by inhibiting JNK and p38 phophorylation.2010
Author(s)
Kawasaki Y, Harashima S, Sasaki M, Mukai E, Nakamura Y, Harada N, Toyoda K, Hamasaki A, Yamane S, Yamada C, Yamada Y, Seino Y, Inagaki N
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Journal Title
Hormone and Metabolic Research
Volume: 42
Pages: 311-317
Related Report
Peer Reviewed
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[Journal Article] Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice.2010
Author(s)
Fujita Y, Hosokawa M, Fujimoto S, Mukai E, Abudukadier A, Obara A, Ogura M, Nakamura Y, Toyoda K, Nagashima K, Seino Y, Inagaki N.
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Journal Title
Diabetologia
Volume: 53
Pages: 1472-1481
Related Report
Peer Reviewed
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[Journal Article] FGF-21 enhances islet engraftment in mouse syngeneic islet transplantation model.
Author(s)
Uonaga, T., Toyoda, K., Okitsu, T., Liu, X.-B., Yamane, S., Uemoto, S., and Inagaki, N.
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Journal Title
Islets.
Volume: 2
Pages: 247-251
Related Report
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[Presentation] Development of non-invasive PET probe for quantifying pancreatic β-cell mass using fluorine-18-labeled exendin-4. 9th International Diabetes Federation Western Pacific Region Congress2012
Author(s)
Fujimoto, H., Toyoda, K., Kimura, H., Saji, H.,Inagaki, N.
Organizer
4th Scientific Meeting of the Asian Association for the Study of Diabetes.
Place of Presentation
Kyoto, Japan
Year and Date
2012-11-27
Related Report
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[Presentation] 膵β細胞GLP-1受容体を標的とするSPECT用イメージングプローブExendin(9-39)誘導体の開発2011
Author(s)
小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
Organizer
第51回日本核医学会学術総会
Place of Presentation
つくば国際会議場(茨城)
Year and Date
2011-10-28
Related Report
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[Presentation] Non-Invasive SPECT Imaging of Pancreatic Islets Targeting Glucagon-Like Peptide-1 Receptors2011
Author(s)
Fujimoto H, Toyoda K, Kimura H, Ogawa Y, Mukai E, Xiaotong Z, Kawashima H, Ueda M, Matsuda H, Hirao K, Saji H, Inagaki N
Organizer
American Diabetes Association 71th Scientific Sessions
Place of Presentation
サン・ディエゴ(米国)
Year and Date
2011-06-30
Related Report
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[Presentation] Development of Non-Invasive PET Probe for Quantifying Pancreatic β-cell mass using Fluorine-18-Labeled Exendin-42011
Author(s)
Toyoda K, Kimura H, Fujimoto H, Xiaotong Z, Mukai E, Ogawa Y, Hirao K, Matsuda H, Kawashima H, Ueda M, Temma T, Saji H, Inagaki, N
Organizer
American Diabetes Association 71th Scientific Sessions
Place of Presentation
サン・ディエゴ(米国)
Year and Date
2011-06-29
Related Report
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[Presentation] GLP-1受容体を標的とするSPECT用膵島イメージングプローブの開発2011
Author(s)
藤本裕之, 豊田健太郎, 木村寛之, 小川祐, 向英里, 庄暁桐, 上田真史, 天満敬, 河嶋秀和, 平尾佳, 松尾洋和, 永川健司, 佐治英郎, 稲垣暢也
Organizer
第54回日本糖尿病学会年次学術集会
Place of Presentation
さっぽろ芸術文化の館(北海道)
Year and Date
2011-05-21
Related Report
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[Presentation] GLP-1受容体を標的とする非侵襲的膵島イメージンのためのPET用プローブの開発2011
Author(s)
豊田健太郎, 木村寛之, 藤本裕之, 小川祐, 向英里, 庄暁桐, 河嶋秀和, 平尾佳, 松尾洋和, 永川健司, 佐治英郎, 稲垣暢也
Organizer
第54回日本糖尿病学会年次学術集会
Place of Presentation
さっぽろ芸術文化の館(北海道)
Year and Date
2011-05-19
Related Report
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[Presentation] GLP-1受容体を標的とする放射性ヨウ素標識イメージングプローブの開発2010
Author(s)
小川祐, 木村寛之, 河嶋秀和, 豊田健太郎, 向英里, 藤本裕之, 平尾佳, 松田洋和, 小野正博, 稲垣暢也, 佐治英郎
Organizer
第50回日本核医学会学術総会
Place of Presentation
埼玉
Year and Date
2010-11-11
Related Report
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[Presentation] Non-invasive PET imaging of pancreatic islets targeting glucagon-like peptide-1 receptors.2010
Author(s)
Toyoda K, Kimura H, Mukai E, Fujimoto H, Ogawa Y, Kawashima H, Ueda M, Temma T, Hirao K, Nagakawa K, Seino Y, Saji H, Inagaki N.
Organizer
8th IDF WPR Congress
Place of Presentation
Busan, Korea
Year and Date
2010-10-20
Related Report
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[Presentation] Non-invasive PET imaging of pancreatic islets targeting glucagon-like peptide-1 receptors.2010
Author(s)
Toyoda K, Kimura H, Mukai E, Fujimoto H, Ogawa Y, Kawashima H, Ueda M, Temma T, Hirao K, Nagakawa K, Seino Y, Saji H, Inagaki N.
Organizer
American Diabetes Association 70th Scientific Sessions
Place of Presentation
Orland, U.S.A.
Year and Date
2010-06-28
Related Report
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[Presentation] Synthesis and evaluation of radioiodinated exendin derivatives for the imaging of GLP-1 receptor expression in pancreatic islets.2010
Author(s)
Kimura H, Ogawa Y, Kawashima H, Mukai E, Toyoda K, Fujimoto H, Hirao K, Ono M, Inagaki N, Saji H.
Organizer
Society of Nuclear Medicine 57th Annual Meeting
Place of Presentation
Tronto, Canada
Year and Date
2010-06-06
Related Report
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[Presentation] Development of Non-Invasive PET Probe for Quantifying Pancreatic B-Cell Mass Using Fluorine-18-Labeled Exendin-4.
Author(s)
Fujimoto H, Toyoda K, Kimura H, Ogawa Y, Mukai E, Zhuang X, Ueda M, Temma T, Hirai M, Matsuda H, Saji H, Inagaki N.
Organizer
9th International Diabetes Federation Western Pacific Region Congress / 4th Scientific Meeting of the Asian Association for the Study of Diabetes.
Place of Presentation
Kyoto, Japan
Related Report
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[Presentation] Development of 123I-labeled exendin derivative binding to GLP-1 receptors for imaging insulinoma by SPECT.
Author(s)
Matsuda H, Kimura H, Ogawa Y, Takagi M, Kon A, Ono M, Toyoda K, Inagaki N, Saji
Organizer
Society of Nuclear Medicine 59th Annual Meeting,
Place of Presentation
Miami, U.S.A
Related Report
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