title: GLP-1 receptor antagonist as a potential probe for pancreatic beta-cell imaging.
abstract: We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic beta-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [(125)I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [(125)I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [(125)I]BH-exendin(9-39) injection into transgenic mice with pancreatic beta-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic beta-cell imaging.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Mukai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kawashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.forename: Konomu
authors.initials: K
authors.lastname: Hirao
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagakawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000818:Animals; D000067757:Glucagon-Like Peptide-1 Receptor; D049452:Green Fluorescent Proteins / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015335:Molecular Probes / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011877:Radionuclide Imaging; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*
chemical_list: C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007457:Iodine Radioisotopes; D015335:Molecular Probes; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D049452:Green Fluorescent Proteins; C083773:exendin (9-39)