title: Fluorescent exendin-4 derivatives for pancreatic β-cell analysis.
abstract: The ability to reliably identify pancreatic β-cells would have far reaching implications for a greater understanding of β-cell biology, measurement of β-cell mass in diabetes, islet transplantation, and drug development. The glucagon-like peptide-1 receptor (GLP1R) is highly expressed on the surface of insulin producing pancreatic β-cells. Using systematic modifications of the GLP1R ligand, exendin-4, we screened over 25 compounds and identified a palette of fluorescent exendin-4 with high GLP1R binding affinity. We show considerable differences in affinity, as well as utility of the top candidates for flow cytometry and microscopy of β-cells. Some of the developed compounds should be particularly useful for basic and translational β-cell research.
authors: Center for Systems Biology, Massachusetts General Hospital , 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, United States.
authors: Susan M
authors: SM
authors: Clardy
authors: Edmund J
authors: EJ
authors: Keliher
authors: James F
authors: JF
authors: Mohan
authors: Matt
authors: M
authors: Sebas
authors: Christophe
authors: C
authors: Benoist
authors: Diane
authors: D
authors: Mathis
authors: Ralph
authors: R
authors: Weissleder
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000077270:Exenatide; D005453:Fluorescence; D000067757:Glucagon-Like Peptide-1 Receptor; D057809:HEK293 Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000737:chemistry; D014688:Venoms / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide