Fluorescent Exendin-4 Derivatives for Pancreatic β-Cell Analysis

The ability to reliably identify pancreatic beta-cells would have far reaching implications for a greater understanding of beta-cell biology, measurement of beta-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 beta-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 beta-cells. Some of the developed compounds should be particularly useful for basic and translational beta-cell research.