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Fluorescent exendin-4 derivatives for pancreatic ?-cell analysis.

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

SUBMITTER: Clardy SM

PROVIDER: S-EPMC4016126 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Fluorescent exendin-4 derivatives for pancreatic β-cell analysis.

Clardy Susan M SM Keliher Edmund J EJ Mohan James F JF Sebas Matt M Benoist Christophe C Mathis Diane D Weissleder Ralph R

Bioconjugate chemistry 20131220 1

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 ...[more]

PMID: 24328216

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