GLP-1 Receptor Mediated Targeting of a Fluorescent Zn<sup>2+</sup> Sensor to Beta Cell Surface for Imaging Insulin/Zn<sup>2+</sup> Release

Daliang Li, Zhijiang Huang, Shiuhwei Chen, Zeping Hu, Wen Hong Li

Research output: Contribution to journalArticle

6 Citations (Scopus)

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<sup>2+</sup> sensor and a truncated exendin 4 peptide for imaging insulin/Zn<sup>2+</sup> release in islet beta cells. In vitro, the conjugate bound to Zn<sup>2+</sup> with high affinity and displayed a robust fluorescence enhancement upon Zn<sup>2+</sup> 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<sup>2+</sup> release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.

Original languageEnglish (US)
Pages (from-to)1443-1450
Number of pages8
JournalBioconjugate Chemistry
Volume26
Issue number8
DOIs
StatePublished - Aug 19 2015

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Insulin
Imaging techniques
Peptides
Islets of Langerhans
Sensors
Cell Tracking
Monitoring
Biomarkers
Medical problems
Chelation
Insulin-Secreting Cells
Labeling
Glucose
Blood Glucose
Glucagon-Like Peptide-1 Receptor
Blood
Fluorescence
Population

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

GLP-1 Receptor Mediated Targeting of a Fluorescent Zn<sup>2+</sup> Sensor to Beta Cell Surface for Imaging Insulin/Zn<sup>2+</sup> Release. / Li, Daliang; Huang, Zhijiang; Chen, Shiuhwei; Hu, Zeping; Li, Wen Hong.

In: Bioconjugate Chemistry, Vol. 26, No. 8, 19.08.2015, p. 1443-1450.

Research output: Contribution to journalArticle

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