Article thumbnail

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

By Daliang Li (1547656), ZhiJiang Huang (1547653), Shiuhwei Chen (1547650), Zeping Hu (538622) and Wen-hong Li (1547647)

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

Topics: Biophysics, Cell Biology, Physiology, Biotechnology, Immunology, Developmental Biology, Space Science, Chemical Sciences not elsewhere classified, beta cell mass, monitoring beta cell mass, monitoring islet beta cells, beta cells, islet beta cells, imaging beta cell function, exendin 4 peptide, insulin, imaging probes, GLP, Beta Cell Surface, Zn, blood glucose level, beta cell function
Year: 2015
DOI identifier: 10.1021/acs.bioconjchem.5b00332.s002
OAI identifier: oai:figshare.com:article/2139745
Provided by: FigShare
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • https://figshare.com/articles/... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.