First quantitative high-throughput screen in zebrafish identifies novel pathways for increasing pancreatic ß-cell mass.
Elife
; 42015 Jul 28.
Article
en En
| MEDLINE
| ID: mdl-26218223
ABSTRACT
Whole-organism chemical screening can circumvent bottlenecks that impede drug discovery. However, in vivo screens have not attained throughput capacities possible with in vitro assays. We therefore developed a method enabling in vivo high-throughput screening (HTS) in zebrafish, termed automated reporter quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this platform quantified cell-specific fluorescent reporters in >500,000 transgenic zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs that increased the number of insulin-producing ß cells in the pancreas. 24 drugs were confirmed as inducers of endocrine differentiation and/or stimulators of ß-cell proliferation. Further, we discovered novel roles for NF-κB signaling in regulating endocrine differentiation and for serotonergic signaling in selectively stimulating ß-cell proliferation. These studies demonstrate the power of ARQiv-HTS for drug discovery and provide unique insights into signaling pathways controlling ß-cell mass, potential therapeutic targets for treating diabetes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pez Cebra
/
Diferenciación Celular
/
Proliferación Celular
/
Células Secretoras de Insulina
/
Descubrimiento de Drogas
/
Ensayos Analíticos de Alto Rendimiento
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos