GLP-1 Receptor Mediated Targeting of a Fluorescent Zn(2+) Sensor to Beta Cell Surface for Imaging Insulin/Zn(2+) Release.
Bioconjug Chem
; 26(8): 1443-50, 2015 Aug 19.
Article
en En
| MEDLINE
| ID: mdl-26121325
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 diabetesa disease affecting â¼9% 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Zinc
/
Células Secretoras de Insulina
/
Exocitosis
/
Imagen Molecular
/
Receptor del Péptido 1 Similar al Glucagón
/
Insulina
Límite:
Animals
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos