Development of the novel diagnostic method for quantification ofpancreatic beta-cell mass by magnetic resonance imaging

开发通过磁共振成像定量胰腺β细胞质量的新诊断方法

• 批准号: 22390185
• 负责人: INAGAKI Nobuya
• 金额: $ 11.98万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390185/
• 关键词: 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

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.

已知在糖尿病的发生和发展过程中，胰腺β细胞的体积会减少。本研究的目的是建立利用磁共振成像技术测量活体β细胞体积的技术。我们首先评估了在有或没有常见的增强剂如Gd溶液的情况下，是否通过MRI的各种分析参数来检测胰岛，然而，它们没有被成像。其次，我们尝试使用新研制的探头进行磁共振成像。我们通过将氟添加到胰腺β细胞上特异表达的胰升糖素样肽-1受体(GLP-1R)的配体Exendin(9-39)上，合成了该探针。然而，与我们的初步实验相反，根本没有检测到任何信号。使用INS-1细胞株进行同样的分析也显示了类似的糟糕结果。这种弱信号的原因被认为是由于与完整的exendins相比，我们的氟标记exendin(9-39)与GLP-1R的亲和力极低。因此，我们合成了新的探针，将氟加到另一种GLP-1R配体exendin-4上，它与完整的exendins具有类似的结合亲和力。我们现在正计划使用这个新的探头进行MRI分析。

项目成果

Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice.

• DOI: 10.2337/db10-1462
• 发表时间: 2011-09
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Himeno T;Kamiya H;Naruse K;Harada N;Ozaki N;Seino Y;Shibata T;Kondo M;Kato J;Okawa T;Fukami A;Hamada Y;Inagaki N;Seino Y;Drucker DJ;Oiso Y;Nakamura J
• 通讯作者: Nakamura J

GLP-1の膵島再生・膵島イメージングへの応用

GLP-1在胰岛再生及胰岛成像中的应用

• 发表时间: 2011
• 期刊: 最新医学
• 作者: 豊田健太郎;稲垣暢也
• 通讯作者: 稲垣暢也

Metformin suppresses hepatic gluconeogenesis and lowers fasting blood glucose levels through reactive nitrogen species in mice

• DOI: 10.1007/s00125-010-1729-5
• 发表时间: 2010-07-01
• 期刊: DIABETOLOGIA
• 影响因子: 8.2
• 作者: Fujita, Y.;Hosokawa, M.;Inagaki, N.
• 通讯作者: Inagaki, N.

Synthesis and evaluation of radioiodinated exendin derivatives for the imaging of GLP-1 receptor expression in pancreatic islets.

用于胰岛 GLP-1 受体表达成像的放射性碘化毒蜥外泌肽衍生物的合成和评估。

• 发表时间: 2010
• 作者: Kimura H;Ogawa Y;Kawashima H;Mukai E;Toyoda K;Fujimoto H;Hirao K;Ono M;Inagaki N;Saji H.
• 通讯作者: Saji H.

膵島イメージング用分子プローブ及びその使用

用于胰岛成像的分子探针及其应用

• 发表时间: 2010