1 research outputs found
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
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