title: GLP-1 Receptor Mediated Targeting of a Fluorescent Zn(2+) Sensor to Beta Cell Surface for Imaging Insulin/Zn(2+) Release.
abstract: The pancreatic islet beta cell plays an essential role in maintaining the normal blood glucose level by releasing insulin. Loss of functional beta cell mass leads to diabetes—a disease affecting ∼9% of the population worldwide. There has been great interest and intense effort in developing imaging probes for monitoring islet beta cells, and glucagon-like peptide-1 receptor (GLP-1R) has emerged as a valuable biomarker for targeting beta cells. However, efforts thus far in GLP-1R mediated beta cell labeling and imaging has largely, if not exclusively, focused on developing imaging probes for monitoring beta cell mass, and few studies have investigated imaging beta cell function (insulin release) through GLP-1R. We now report the design and synthesis of a bioconjugate, ZIMIR-Ex4(9-39), that consists of a fluorescent Zn(2+) sensor and a truncated exendin 4 peptide for imaging insulin/Zn(2+) release in islet beta cells. In vitro, the conjugate bound to Zn(2+) with high affinity and displayed a robust fluorescence enhancement upon Zn(2+) chelation. When added to beta cells at submicromolar concentration, ZIMIR-Ex4(9-39) rapidly labeled cell surface in minutes to report the dynamics of insulin/Zn(2+) release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.
authors.affiliation: †Departments of Cell Biology and of Biochemistry, ‡Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9039, United States.
authors.forename: Daliang
authors.initials: D
authors.lastname: Li
authors.affiliation: †Departments of Cell Biology and of Biochemistry, ‡Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9039, United States.
authors.forename: ZhiJiang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: †Departments of Cell Biology and of Biochemistry, ‡Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9039, United States.
authors.forename: Shiuhwei
authors.initials: S
authors.lastname: Chen
authors.affiliation: †Departments of Cell Biology and of Biochemistry, ‡Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9039, United States.
authors.forename: Zeping
authors.initials: Z
authors.lastname: Hu
authors.affiliation: †Departments of Cell Biology and of Biochemistry, ‡Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9039, United States.
authors.forename: Wen-hong
authors.initials: WH
authors.lastname: Li
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D005456:Fluorescent Dyes / Q000737:chemistry; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D041681:NIH 3T3 Cells; D015032:Zinc / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D015032:Zinc