Back to Search
Start Over
GLP-1 Receptor Mediated Targeting of a Fluorescent Zn2+ Sensor to Beta Cell Surface for Imaging Insulin/Zn2+ Release
- Source :
- Bioconjugate Chemistry. 26:1443-1450
- Publication Year :
- 2015
- Publisher :
- American Chemical Society (ACS), 2015.
-
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(2+) sensor and a truncated exendin 4 peptide for imaging insulin/Zn(2+) release in islet beta cells. In vitro, the conjugate bound to Zn(2+) with high affinity and displayed a robust fluorescence enhancement upon Zn(2+) 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(2+) release with high spatiotemporal resolution. Future explorations of this approach may lead to probes for tracking beta cell function using different imaging modalities.
- Subjects :
- endocrine system
medicine.medical_treatment
Population
Biomedical Engineering
Pharmaceutical Science
Bioengineering
Peptide
Biosensing Techniques
Exocytosis
Glucagon-Like Peptide-1 Receptor
Mice
Insulin-Secreting Cells
Insulin Secretion
medicine
Animals
Insulin
Receptor
education
Beta (finance)
Cells, Cultured
Glucagon-like peptide 1 receptor
Fluorescent Dyes
Pharmacology
chemistry.chemical_classification
education.field_of_study
geography
geography.geographical_feature_category
Chemistry
Organic Chemistry
Islet
Molecular Imaging
Cell biology
Zinc
Microscopy, Fluorescence
Biochemistry
NIH 3T3 Cells
Beta cell
Biotechnology
Subjects
Details
- ISSN :
- 15204812 and 10431802
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....f87cca5ec66551250c6f0a473320986a