TY - JOUR
T1 - GLP-1 Receptor Mediated Targeting of a Fluorescent Zn2+ Sensor to Beta Cell Surface for Imaging Insulin/Zn2+ Release
AU - Li, Daliang
AU - Huang, Zhijiang
AU - Chen, Shiuhwei
AU - Hu, Zeping
AU - Li, Wen Hong
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - 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 Zn2+ sensor and a truncated exendin 4 peptide for imaging insulin/Zn2+ release in islet beta cells. In vitro, the conjugate bound to Zn2+ with high affinity and displayed a robust fluorescence enhancement upon Zn2+ 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/Zn2+ release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.
AB - 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 Zn2+ sensor and a truncated exendin 4 peptide for imaging insulin/Zn2+ release in islet beta cells. In vitro, the conjugate bound to Zn2+ with high affinity and displayed a robust fluorescence enhancement upon Zn2+ 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/Zn2+ release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.
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U2 - 10.1021/acs.bioconjchem.5b00332
DO - 10.1021/acs.bioconjchem.5b00332
M3 - Article
C2 - 26121325
AN - SCOPUS:84939614822
SN - 1043-1802
VL - 26
SP - 1443
EP - 1450
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 8
ER -